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Supplementary Material S1: Reactions and enzymes of metabolic pathways in H. salinarum. Reaction-Identifiers and equations have been retrieved from the KEGG ligand database (Kanehisa et al. 2004). Shaded reactions likely exist in H. salinarum. While enzyme genes have been assigned for reactions highlighted in green, experimental but no genetic evidences are currently available for reactions with gray shading. Experimental evidences such as NMR studies or enzyme activity tests from external references (PMID) have been included within the comment field. (Supplementary Material S1 will be published within Halolex: http://www.halolex.mpg.de) 1 Glycolytic pathways Embden-Meyerhof pathway and gluconeogenesis react_id subsystem EC-No reaction status genes references comment R00199 C 2.7.9.2 ATP + Pyruvate + H2O <=> AMP + Phosphoenolpyruvate + Orthophosphate R00200 C 2.7.1.40 ATP + Pyruvate <=> ADP + Phosphoenolpyruvate YES secure R00206 C 2.7.9.1 ATP + Pyruvate + Orthophosphate <=> AMP + Phosphoenolpyruvate + Pyrophosphate YES 2256927 OE1500R insecure 9827332 NMR; labeled pyruvate converted to glc if TCA cycle blocked; R00299 C 2.7.1.1 2.7.1.2 ATP + D-Glucose <=> ADP + D-Glucose 6-phosphate 2256927 YES OE4691R 3255682 insecure 6642538 NMR; labeled glc converted to glc-6P; neg_enz_activ for EC 2.7.1.1; R00303 C 3.1.3.9 D-Glucose 6-phosphate + H2O <=> D-Glucose + Orthophosphate YES insecure 3255682 9827332 pos_enz_activ; NMR; no_genet_evid; labeled pyruvate converted to glc if TCA cycle blocked; R00341 C 4.1.1.49 ATP + Oxaloacetate <=> ADP + Phosphoenolpyruvate + CO2 NO unlikely - no blastp hit with A. pernix enz.; R00346 C 4.1.1.38 Pyrophosphate + Oxaloacetate <=> Orthophosphate + Phosphoenolpyruvate + CO2 NO unlikely R00431 C 4.1.1.32 GTP + Oxaloacetate <=> GDP + Phosphoenolpyruvate + CO2 NO unlikely R00658 C 4.2.1.11 2-Phospho-D-glycerate <=> Phosphoenolpyruvate + H2O YES secure R00756 C 2.7.1.11 ATP + D-Fructose 6-phosphate <=> ADP + D-Fructose 1,6-bisphosphate NO unlikely YES secure OE1500R 2256927 9827332 OE1495R 3255682 2256927 3255682 OE2640F 6642538 9827332 3255682 6642538 NMR; labeled pyruvate converted to glc if TCA cycle blocked; pos_enz_activ; pos_enz_activ; NMR; EA low compared with H. mediterranei and H. vallismortis; labeled pyruvate converted to glc if TCA cycle blocked; neg_enz_activ; 1 YES secure 2256927 3255682 6642538 9827332 pos_enz_activ; NMR; high activ. in glc-grown cells; low activ. in glycerol- and pyruvate-grown cells; labeled pyruvate converted to glc if TCA cycle blocked; - no homology to and T. tenax enzymes; R00762 C 3.1.3.11 D-Fructose 1,6-bisphosphate + H2O <=> D-Fructose 6-phosphate + Orthophosphate R00764 C 2.7.1.90 Pyrophosphate + D-Fructose 6-phosphate <=> NO Orthophosphate + D-Fructose 1,6unlikely bisphosphate R00771 C 5.3.1.9 D-Glucose 6-phosphate <=> D-Fructose 6-phosphate YES secure R00866 C 2.7.1.3 ATP + D-Fructose <=> ADP + D-Fructose 1-phosphate NO unlikely R01015 C 5.3.1.1 D-Glyceraldehyde 3-phosphate <=> Glycerone phosphate YES secure 2256927 9827332 NMR; labeled pyruvate converted to glc if TCA cycle blocked; R01058 C 1.2.1.9 D-Glyceraldehyde 3-phosphate + NADP+ + H2O <=> 3-Phospho-D-glycerate + NADPH OE2133R YES OE2190R 2256927 insecure OE2367F 9827332 OE4529F NMR; labeled pyruvate converted to glc if TCA cycle blocked; R01061 C 1.2.1.12 1.2.1.59 D-Glyceraldehyde 3-phosphate + Orthophosphate + NAD+ <=> YES 3-Phospho-D-glyceroyl phosphate + NADH + secure H+ 2256927 3255682 OE1154F 6642538 9827332 R01063 C 1.2.1.13 1.2.1.59 D-Glyceraldehyde 3-phosphate + Orthophosphate + NADP+ <=> YES 3-Phospho-D-glyceroyl phosphate + NADPH secure + H+ OE1154F R01068 C 4.1.2.13 D-Fructose 1,6-bisphosphate <=> Glycerone phosphate + D-Glyceraldehyde 3phosphate YES secure 2256927 OE1472F 3255682 OE2019F 6642538 9827332 R01512 C 2.7.2.3 ATP + 3-Phospho-D-glycerate <=> ADP + 3-Phospho-D-glyceroyl phosphate YES secure OE2745R R01515 C 3.6.1.7 3-Phospho-D-glyceroyl phosphate + H2O <=> 3-Phospho-D-glycerate + Orthophosphate R01518 C 5.4.2.1 R02185 C R03232 C OE2020F 2256927 3255682 OE3792F 6642538 9827332 OE2500R 2256927 3255682 6642538 9827332 pos_enz_activ; NMR; EA low compared with H. mediterranei and H. vallismortis; labeled pyruvate converted to glc-6P if TCA cycle blocked; EC 1.2.1.59 typ. for arch.; pos_enz_activ; NMR; EA (EC 1.2.1.12) low compared with H. mediterranei and H. vallismortis; labeled pyruvate converted to glc if TCA cycle blocked; EC 1.2.1.59 typ. for arch.; NMR; labeled pyruvate converted to glc if TCA cycle blocked; pos_enz_activ; NMR; EA low compared with H. mediterranei and H. vallismortis; labeled pyruvate converted to glc if TCA cycle blocked; 2256927 9827332 NMR; labeled pyruvate converted to glc if TCA cycle blocked; NO unlikely - no homology to A. fulgidus enzyme; 2-Phospho-D-glycerate <=> 3-Phospho-D-glycerate YES secure 2256927 9827332 NMR; labeled pyruvate converted to glc if TCA cycle blocked; 2.7.1.63 (Phosphate)n + D-Glucose <=> (Phosphate)n + D-Glucose 6-phosphate NO unlikely 2.7.1.69 Protein N(pai)-phosphohistidine + D-Fructose NO <=> unlikely OE3653R 2 Protein histidine + D-Fructose 1-phosphate R05805 C 2.7.1.146 ADP + D-Fructose 6-phosphate <=> AMP + D-Fructose 1,6-bisphosphate NO unlikely R10000 C 2.7.1.56 ATP + D-Fructose 1-phosphate <=> ADP + D-Fructose 1,6-bisphosphate NO unlikely - no homology to P. furiosus, T. litoralis and T. zilligii enzymes; Entner-Douderoff pathway react_id subsystem EC-No reaction status genes references comment R00300 C D-Glucose + NAD+ <=> 1.1.1.118 NO D-Glucono-1,5-lactone + 1.1.1.47 unlikely NADH R00305 C 1.1.5.2 D-Glucose + Acceptor <=> NO D-Glucono-1,5-lactone + unlikely Reduced acceptor R00835 C 1.1.1.49 D-Glucose 6-phosphate + NADP+ <=> YES D-Glucono-1,5-lactone insecure 6-phosphate + NADPH + H+ 11271421 5780095 pos_enz_activ; no_genet_evid; enz_activ. with NAD and NADP; kinet. mech. studied; 10650712 R01519 C 3.1.1.17 D-Glucono-1,5-lactone + YES H2O <=> insecure D-Gluconic acid 2256927 R01538 C 4.2.1.39 D-Gluconic acid <=> 2-Dehydro-3-deoxy-Dgluconate + H2O YES likely OE1664R 16794308 OE1664R is homolog to Sulfolobus enzyme (SSO3198, PMID:16794308); OE1664R is part of ED pathway gene cluster; no 11271421 enzyme activity observed in indirect test for 3-step ED reaction sequence from gluconate, but enzyme activity proven for H. 3255682 mediterranei; 15869466 R01541 C 2.7.1.45 ATP + 2-Dehydro-3deoxy-D-gluconate <=> ADP + 2-Dehydro-3deoxy-6-phospho-Dgluconate YES likely 11271421 enz. activ. not found (test for a 3 step ED react. seq. done), but enz. activ. proven for H. mediterranei; likely homologue to H. OE1266R 3255682 mediterranei enz. found; 15869466 R02035 C 3.1.1.31 D-Glucono-1,5-lactone 6-phosphate + H2O <=> 6-Phospho-D-gluconate NO unlikely R02036 C 4.2.1.12 6-Phospho-D-gluconate <=> 2-Dehydro-3-deoxy-6phospho-D-gluconate + H2O NO unlikely R05605 C 4.1.2.14 2-Dehydro-3-deoxy-6- YES 2256927 neg_enz_activ; hasal glc-1-dh does not prefer NAD+ as coenzyme; all known glc-1-dh seq seem to be assign. to EC 1.1.1.47 using beta-glucose; NMR; no_genet_evid; labeled glc metabolized to gluconate in glc-grown HS cells; OE1665R 10760168 OE1665R is homolog to bifunctional Sulfolobus KD(P)G aldolase (SSO3197, PMID:15869466); OE1665R is part of ED 3 phospho-D-gluconate <=> D-Glyceraldehyde 3phosphate + Pyruvate likely R10001 C D-Glucose + NADP+ 1.1.1.119 <=> YES 1.1.1.47 D-Glucono-1,5-lactone + likely NADPH R10002 C 2-Dehydro-3-deoxy-6phospho-D-gluconate <=> D-Glyceraldehyde + Pyruvate 4.1.2.20 11271421 pathway gene cluster; H. salinarum contains no homolog of the classic KDPG aldolase, which is present in other haloarchaea, 3255682 e.g. in H. mediterranei (GenBank: AAB40121); no enzyme activity observed in indirect test for 3-step ED reaction sequence 16794308 from gluconate but enzyme activity proven for H. mediterranei; 15869466 OE1669F 2256927 8925901 pos_enz_activ; NMR; labeled glucose is metabolized to gluconate in glucose-grown H. salinarum cells (PMID:2256927); NAD(P)-glucose dehydrogenase from H. mediterranei has been characterized and N-terminally sequenced (OE1669F matches) (PMID:8925901); OE1669F is part of ED pathway gene cluster; NO unlikely 2 Pentose-phosphate pathway and pentose metabolism react_id subsystem EC-No reaction status genes references comment R00024 C D-Ribulose 1,5-bisphosphate + CO2 + NO 4.1.1.39 H2O <=> unlikely 2 3-Phospho-D-glycerate - 3255682 negative enzyme activity; reaction of novel archaeal AMP recycling pathway; no homolog to N. pharaonis 17303759 RuBisCO (NP2770A); R00835 C 1.1.1.49 D-Glucose 6-phosphate + NADP+ <=> YES D-Glucono-1,5-lactone 6-phosphate + insecure NADPH + H+ - 11271421 5780095 pos_enz_activ; no_genet_evid; enz_activ. with NAD and NADP; kinet. mech. studied; 10650712 R01056 C 5.3.1.6 D-Ribose 5-phosphate <=> D-Ribulose 5-phosphate YES secure OE4185F R01067 C 2.2.1.1 D-Fructose 6-phosphate + DGlyceraldehyde 3-phosphate <=> D-Erythrose 4-phosphate + DXylulose 5-phosphate NO unlikely - R01523 C 2.7.1.19 ATP + D-Ribulose 5-phosphate <=> ADP + D-Ribulose 1,5-bisphosphate NO questionable R01528 C 1.1.1.44 6-Phospho-D-gluconate + NADP+ <=> D-Ribulose 5-phosphate + CO2 + NADPH + H+ YES insecure OE4581F 3255682 enz. activ. of H. vallismortui and H. mediterranii inhib. by salt; only N-terminal domain conserved; C-terminal 6PGD-domain only feable conserved; R01529 C 5.1.3.1 D-Ribulose 5-phosphate <=> D-Xylulose 5-phosphate NO unlikely - - no homologue to M. jannaschii enzyme; R01641 C 2.2.1.1 D-Sedoheptulose 7-phosphate + DGlyceraldehyde 3-phosphate <=> NO unlikely - - no homologue to two M. jannaschii enzymes; - no homologue to two M. jannaschii enzymes; 3255682 positive enzyme activity but no genetic evidence; genetic evidence (OE4651F) for novel archaeal reaction from 15375115 PRPP to ribulose 1,5-biphosphate found; 4 D-Ribose 5-phosphate + D-Xylulose 5-phosphate R01827 C 2.2.1.2 D-Sedoheptulose 7-phosphate + DGlyceraldehyde 3-phosphate <=> NO D-Erythrose 4-phosphate + D-Fructose unlikely 6-phosphate - R02035 C D-Glucono-1,5-lactone 6-phosphate + NO 3.1.1.31 H2O <=> unlikely 6-Phospho-D-gluconate - R05338 C - D-Ribulose 5-phosphate + Formaldehyde <=> D-Arabino-6-hexulose 3-phosphate NO questionable ribulose monophosphate pathway substitutes the missing pentose phosphate pathway in several archaea; no 16237021 homolog to 6-phospho-3-hexuloisomerase (COG0794) and 3-hexulose-6-phosphate synthase (COG0269) found 16788179 in haloarchaea; R05339 C - D-Arabino-6-hexulose 3-phosphate <=> D-Fructose 6-phosphate NO questionable ribulose monophosphate pathway substitutes the missing pentose phosphate pathway in several archaea; no 16237021 homolog to 6-phospho-3-hexuloisomerase (COG0794) and 3-hexulose-6-phosphate synthase (COG0269) found 16788179 in haloarchaea; R10008 C - 5-Phospho-alpha-D-ribose 1diphosphate <=> D-Ribulose 1,5-bisphosphate YES secure R10009 P - AMP + Orthophosphate <=> NO D-Ribose 1,5-bisphosphate + Adenine unlikely - R10010 P - D-Ribose 1,5-bisphosphate <=> D-Ribulose 1,5-bisphosphate OE3610R 17303759 YES likely - no homologue to M. jannaschii, T. acidophilum and T. volcanium enzymes; OE4651F 15375115 ribulose 1,5-biphosphate produced from PRPP and not from not ribulose 5-phosphate in archaea; 17303759 reaction of novel archaeal AMP recycling pathway; no homolog to N. pharaonis AMP phosphorylase (NP3958A); reaction of novel archaeal AMP recycling pathway; all pathway enzymes encoded by N. pharaonis, but only ribose-1,5-biphosphate isomerase encoded by H. salinarum; 3 Glycerol metabolism react_id subsystem EC-No reaction status genes references comment C 3.1.3.21 sn-Glycerol 3-phosphate + H2O <=> Glycerol + Orthophosphate NO unlikely - - Dunaliella enz. acts on sn-glycerol 1-phosphate, but also less rapidly on sn-glycerol 3phosphate; R00842 C 1.1.1.8 1.1.1.94 sn-Glycerol 3-phosphate + NAD+ <=> NO Glycerone phosphate + NADH + unlikely H+ - - EC 1.1.1.94: no homologue to M. thermoautotrophicum and A. fulgidus enz.; R00844 C 1.1.1.94 sn-Glycerol 3-phosphate + NADP+ <=> NO Glycerone phosphate + NADPH + unlikely H+ - - no homologue to M. thermoautotrophicum and A. fulgidus enz.; R00847 C 2.7.1.30 ATP + Glycerol <=> ADP + sn-Glycerol 3-phosphate OE3762R 3255682 3700337 radioact; NMR; signals from labeled glycerol found in several aa and isoprenoids; EA test only performed for H. mediterranei and H. vallismortis yet (pos. result); R00841 YES secure 5 R00848 C 1.1.99.5 sn-Glycerol 3-phosphate + FAD <=> Glycerone phosphate + FADH2 YES secure OE3763F OE3764F OE3765F 3700337 radioact; NMR; signals from labeled glycerol found in several aa and isoprenoids; H. salinarum only arch. with this enz.; enz. complex with 3 subunits pred.; R00849 C 1.1.99.5 sn-Glycerol 3-phosphate + Acceptor <=> Glycerone phosphate + Reduced acceptor YES secure OE3763F OE3764F OE3765F 3700337 radioact; NMR; signals from labeled glycerol found in several aa and isoprenoids; H. salinarum only arch. with this enz.; enz. complex with 3 subunits pred.; R01010 C 3.1.3.1 Glycerone phosphate + H2O <=> YES Glycerone + Orthophosphate secure OE5192R - H. salinarum only arch. with this enz.; R01011 C 2.7.1.29 ATP + Glycerone <=> ADP + Glycerone phosphate NO unlikely - R01015 C 5.3.1.1 D-Glyceraldehyde 3-phosphate <=> Glycerone phosphate YES secure OE2500R 2256927 9827332 NMR; labeled pyruvate converted to glc if TCA cycle blocked; R01034 C 1.1.1.6 Glycerol + NAD+ <=> Glycerone + NADH YES secure OE5160F 3255682 pos_enz_activ; high glycerol dh activ. found in H. salinarum, but no EA in H. mediterranei and H. vallismortis; H. salinarum only arch. with this enz.; R01036 C 1.1.1.1 1.1.1.21 Glycerol + NAD+ <=> YES D-Glyceraldehyde + NADH + H+ insecure OE3563R OE4674F - H. salinarum and Sulfolobus only arch. with this enz.; R01039 C 1.1.1.156 Glycerol + NADP+ <=> Glycerone + NADPH + H+ YES insecure OE5160F - as EC 1.1.1.6, only NADP+ as cofact.; R01041 C 1.1.1.1 1.1.1.2 1.1.1.21 1.1.1.72 Glycerol + NADP+ <=> D-Glyceraldehyde + NADPH + H+ YES insecure OE3563R OE4674F - H. salinarum and Sulfolobus only arch. with this enz.; R01059 C 2.7.1.28 ATP + D-Glyceraldehyde <=> ADP + D-Glyceraldehyde 3phosphate NO unlikely - R01514 C 2.7.1.31 ATP + D-Glycerate <=> ADP + 3-Phospho-D-glycerate NO unlikely - R01752 C 1.2.1.3 D-Glyceraldehyde + NAD+ + H2O <=> D-Glycerate + NADH + H+ YES secure OE2133R OE2190R OE2367F OE4529F R05679 C 1.1.1.261 Glycerol 1-phosphate + NAD+ <=> Glycerone phosphate + NADH + H+ YES secure OE1602F 9419225 enz. requ. for formation of sn-glycerol 1-phosphate used for arch.-spec. lipids; stereospec. diff. from glycerol 3-phosphate dh (EC 1.1.1.8); R05680 C 1.1.1.261 Glycerol 1-phosphate + NADP+ <=> YES Glycerone phosphate + NADPH + secure H+ OE1602F - enz. requ. for formation of arch.-spec. glycero-1-phosphate used for phospholipids; stereospec. diff. from EC sn-glycerol-3-phosphate dh; 6 4 Pyruvate metabolism and tricarboxylic acid cycle Pyruvate metabolism react_id subsystem EC-No reaction status genes references R00014 C 1.2.4.1 2.2.1.6 2-(alphaHydroxyethyl)thiamine diphosphate + CO2 <=> Thiamin diphosphate + Pyruvate R00196 C 1.1.2.3 (S)-Lactate + 2 Ferricytochrome NO c <=> unlikely Pyruvate + 2 Ferrocytochrome c R00199 C 2.7.9.2 ATP + Pyruvate + H2O <=> YES AMP + Phosphoenolpyruvate + secure Orthophosphate OE1500R R00200 C 2.7.1.40 ATP + Pyruvate <=> ADP + Phosphoenolpyruvate OE1495R 3255682 R00206 C 2.7.9.1 ATP + Pyruvate + Orthophosphate <=> YES 2256927 OE1500R AMP + Phosphoenolpyruvate + insecure 9827332 Pyrophosphate R00207 C 1.2.3.3 Pyruvate + Orthophosphate + Oxygen <=> Acetyl phosphate + H2O2 + CO2 R00210 C 1.2.1.51 Pyruvate + CoA + NADP+ <=> NO Acetyl-CoA + CO2 + NADPH unlikely R00211 C 1.2.3.6 Pyruvate + CoA + Oxygen <=> NO H2O2 + Acetyl-CoA + CO2 unlikely R00212 C 2.3.1.54 Acetyl-CoA + Formate <=> CoA + Pyruvate R00214 C 1.1.1.38 (S)-Malate + NAD+ <=> 1.1.1.39 Pyruvate + CO2 + NADH 4.1.1.3 YES likely OE3308F - R00216 C 1.1.1.40 (S)-Malate + NADP+ <=> 4.1.1.3 Pyruvate + CO2 + NADPH YES secure OE3308F R00217 C 1.1.1.38 Oxaloacetate <=> 1.1.1.40 Pyruvate + CO2 4.1.1.3 YES likely OE3308F - R00220 C 4.3.1.19 L-Serine <=> Pyruvate + NH3 NO unlikely YES secure comment TU_oxdhA1B_dsa_lpdA; 4 subunits likely to form a 2-oxoacid dehydrogenase complex; not pyruvate or 2-oxoglutarate dh 15556640 complex (lipoic acid absent in H. salinarum pyruvate and 2-oxoglutarate synthase); 2-oxoacid dehydrogenase complex 6266826 might be involved in branched-chain amino acid degradation as in T. acidophilum; 2256927 9827332 NMR; labeled pyruvate converted to glc if TCA cycle blocked; pos_enz_activ; NMR; labeled pyruvate converted to glc if TCA cycle blocked; NO unlikely 6266826 flavin nucleotides absent in Hasal pyruvate synthase; enzyme purified from Euglena (PNO_EUGGR); NO unlikely 8157586 9827332 YES OE3941F insecure enz. activ. only tested with NADP yet; EC 4.1.1.3 not likely; pos_enz_activ; NMR; NADP-dep. malic enz_activ found; 7% of labeled pyruvate entering TCA cycle converted back to pyruvate by malic enz.; H. salinarum only archaea with this enz.; EC 4.1.1.3 not likely; malic enz. (EC 1.1.1.38/40) often also decarb. added oxaloacetate; EC 4.1.1.3 not likely; NMR; Ser signals detected from labeled substrates; pathways via hydroxypyruvate/3P-hydroxypyruvate incomplete; pathway via 3P-hydroxypyruvate likely, since genes for EC 1.1.1.95 and EC 3.1.3.3 adjacent to each other; missing EC 7 2.6.1.52 potentially coded by OE4391F; serine dehydratation to pyruvate by EC 4.3.1.19 might be possible; 4.1.1.1 Pyruvate <=> Acetaldehyde + CO2 NO unlikely R00258 C 2.6.1.2 L-Alanine + 2-Oxoglutarate <=> Pyruvate + L-Glutamate YES secure R00341 C ATP + Oxaloacetate <=> 4.1.1.49 ADP + Phosphoenolpyruvate + CO2 NO unlikely - R00344 C 6.4.1.1 ATP + Pyruvate + HCO3- <=> ADP + Orthophosphate + Oxaloacetate YES insecure 11195096 NMR; 10\\% of labeled pyruvate flows into TCA cycle via PYC; haloarchaea do not encode archaeal-type pyruvate 8157586 carboxylase (MJ1229/MJ1231); OE3177F is a biotin carboxylase, but the enzyme is more likely involved in propionate 9827332 metabolism; N. pharaonis homolog found within fatty-acid degradation cluster; R00345 C 4.1.1.31 Orthophosphate + Oxaloacetate <=> NO H2O + Phosphoenolpyruvate + unlikely CO2 R00346 C 4.1.1.38 Pyrophosphate + Oxaloacetate <=> Orthophosphate + Phosphoenolpyruvate + CO2 R00369 C L-Alanine + Glyoxylate <=> 2.6.1.44 Pyruvate + Glycine R00400 C 2.6.1.12 L-Alanine + Oxaloacetate <=> Pyruvate + L-Aspartate NO unlikely R00431 C GTP + Oxaloacetate <=> 4.1.1.32 GDP + Phosphoenolpyruvate + CO2 NO unlikely R00703 C 1.1.1.27 (S)-Lactate + NAD+ <=> Pyruvate + NADH + H+ R01196 C 1.2.7.1 Reduced ferredoxin + AcetylCoA + CO2 <=> YES Oxidized ferredoxin + Pyruvate secure + CoA 6266826 OE2622R 6266827 OE2623R 8157586 9827332 R01698 C 1.8.1.4 Dihydrolipoamide + NAD+ <=> Lipoamide + NADH YES secure OE4116F R02569 C 2.3.1.12 Acetyl-CoA + Dihydrolipoamide <=> NO unlikely R00224 C OE1755F 8157586 OE1944R 9827332 OE2619F NMR; NMR studies indicate that Ala is not synthesized from pyruvate by glutamate:pyruvate transaminase (alanine aminotransferase, EC 2.6.1.2), but by aspartate:pyruvate transaminase (aspartate aminotransferase, EC 2.6.1.1) (PMID: 8157586); Ala signals were detected from labeled glycerol (if Ala was omitted from the growth medium), but not from labeled acetate (PMID: 3700337); labeled pyruvate was converted to Ala primarly under anaerobic conditions (TCA cycle less active) and in absence of glucose in the growth medium (PMID: 8157586); no blastp hit with A. pernix enz.; NO unlikely YES OE4391F insecure YES insecure 8157586 9827332 NMR; serine--pyruvate aminotransferase (EC 2.6.1.51) might also function as alanine--glyoxylate aminotransferase (EC 2.6.1.44) as shown for the human enzyme; Ala signals were detected from labeled glycerol (if Ala was omitted from the growth medium), but not from labeled acetate (PMID: 3700337); labeled pyruvate was converted to Ala primarly under anaerobic conditions (TCA cycle less active) and in absence of glucose in the growth medium (PMID: 8157586); pos_enz_activ; NMR; no_genet_evid; NADH-dep. EA proven in HS cell extract; labeled pyruvate converted to lactate under anaerobic condit.; pos_enz_activ; NMR; enz. complex with 2 subunits proven; cat. cycle of the enzyme invest.; 90% of labeled pyruvate flows into TCA cycle via POR; only 53% of acetyl-CoA produced from labeled pyruvate, rest generated endogenously; haloarchaea are the only archaea with this enzyme, which is secure to function as a dihydrolipoamide dehydrogenase in 15556640 reactions of a 2-oxoacid dehydrogenase complex (TU_oxdhA1B_dsa_lpdA); not part of pyruvate or 2-oxoglutarate 6266826 dehydrogenase complex; 15556640 haloarchaea are the only archaea with a dihydrolipoamide S-acyltransferase (EC 2.3.1.-), which is likely to function in 6266826 reactions of a 2-oxoacid dehydrogenase complex (TU_oxdhA1B_dsa_lpdA); not part of pyruvate (EC 2.3.1.12) or 2- 8 CoA + SAcetyldihydrolipoamide R03145 C R03270 C oxoglutarate (EC 2.3.1.61) dehydrogenase complex; 1.2.2.2 Ferricytochrome b1 + Pyruvate + H2O <=> Ferrocytochrome b1 + Acetate + CO2 YES insecure 8157586 1.2.4.1 2-(alphaHydroxyethyl)thiamine diphosphate + Lipoamide <=> S-Acetyldihydrolipoamide + Thiamin diphosphate NO unlikely TU_oxdhA1B_dsa_lpdA; 4 subunits likely to form a 2-oxoacid dehydrogenase complex; not pyruvate or 2-oxoglutarate dh 15556640 complex (lipoic acid absent in H. salinarum pyruvate and 2-oxoglutarate synthase); 2-oxoacid dehydrogenase complex 6266826 might be involved in branched-chain amino acid degradation as in T. acidophilum; NMR; no_genet_evid; acetate signals found from labeled pyruvate if growth without glc; Tricarboxylic acid and glyoxylate cycle react_id subsystem EC-No reaction status genes references comment YES secure 4393394 5058691 OE3634F 5780095 5802601 9827332 Oxalosuccinate <=> 2-Oxoglutarate + CO2 YES secure OE3634F 1.1.1.37 (S)-Malate + NAD+ <=> Oxaloacetate + NADH + H+ YES secure OE4323F 5780095 9827332 pos_enz_activ; NMR; 13C NMR studies with labeled pyruvate fully consistent with active TCA cycle; R00351 C 2.3.3.3 2.3.3.1 Citrate + CoA <=> Acetyl-CoA + H2O + Oxaloacetate YES 5780095 OE3934R insecure 9827332 pos_enz_activ; NMR; 13C NMR studies with labeled pyruvate fully consistent with active TCA cycle; R00352 C 2.3.3.8 ATP + Citrate + CoA <=> ADP + Orthophosphate + AcetylCoA + Oxaloacetate YES OE1942F insecure can be dissoc. into compon., 2 are ident. with EC 4.1.3.34 (found by sim. search) and EC 6.2.1.18; R00354 C 4.1.3.34 (3S)-Citryl-CoA <=> Acetyl-CoA + Oxaloacetate YES secure compon. of EC 2.3.3.8 and EC 4.1.3.6; H. salinarum only archaea with this enz.; R00362 C 4.1.3.6 Citrate <=> Acetate + Oxaloacetate YES OE1942F insecure can be dissoc. into compon., 2 are ident. with EC 2.8.3.10 and EC 4.1.3.34 (found by sim. search); R00405 C 6.2.1.5 ATP + Succinate + CoA <=> ADP + Orthophosphate + Succinyl-CoA YES secure pos_enz_activ; NMR; enz. complex with 2 subunits pred.; 13C NMR studies with labeled pyruvate fully consistent with active TCA cycle; R00407 C 3.1.2.3 Succinyl-CoA + H2O <=> CoA + Succinate NO unlikely R00408 C 1.3.99.1 Succinate + FAD <=> FADH2 + Fumarate YES secure R00267 C Isocitrate + NADP+ <=> 1.1.1.42 2-Oxoglutarate + CO2 + NADPH + H+ R00268 C 1.1.1.42 R00342 C OE1942F - OE3195F 5780095 OE3196F 9827332 OE2865R 5780095 OE2866R pos_enz_activ; NMR; first enz_act (EC 1.1.1.42) tested; later enz. purified, enz_act measured and inactivation investig.; 13C NMR studies with labeled pyruvate fully consistent with active TCA cycle; pos_enz_activ; enz. complex with 4 subunits pred.; 9 OE2867R OE2868R R00412 C 1.3.99.1 Succinate + Acceptor <=> Fumarate + Reduced acceptor YES secure OE2865R OE2866R 5780095 OE2867R 9827332 OE2868R pos_enz_activ; NMR; enz. complex with 4 subunits pred.; 13C NMR studies with labeled pyruvate fully consistent with active TCA cycle; R00432 C 6.2.1.4 GTP + Succinate + CoA <=> GDP + Orthophosphate + Succinyl-CoA YES OE3195F 5780095 insecure OE3196F 9827332 pos_enz_activ; NMR; enz. complex with 2 subunits pred.; 13C NMR studies with labeled pyruvate fully consistent with active TCA cycle; R00472 C 2.3.3.9 (S)-Malate + CoA <=> Acetyl-CoA + H2O + Glyoxylate YES insecure 5780095 pos_enz_activ; no_genet_evid; R00479 C 4.1.3.1 Isocitrate <=> Succinate + Glyoxylate YES insecure 5780095 pos_enz_activ; no_genet_evid; R00621 C 1.2.4.2 2-Oxoglutarate + Thiamin diphosphate <=> NO 3-Carboxy-1-hydroxypropyl-ThPP unlikely + CO2 R00709 C Isocitrate + NAD+ <=> 4393394 YES 1.1.1.41 2-Oxoglutarate + CO2 + NADH + OE3634F 5058691 insecure H+ 5802601 R01082 C 4.2.1.2 (S)-Malate <=> Fumarate + H2O YES secure OE2935R R01197 C 1.2.7.3 Reduced ferredoxin + SuccinylCoA + CO2 <=> Oxidized ferredoxin + 2Oxoglutarate + CoA YES secure 5780095 OE1710R 6266826 OE1711R 6266827 9827332 R01322 C ATP + Citrate + CoA <=> 6.2.1.18 ADP + Orthophosphate + (3S)Citryl-CoA R01323 C 2.8.3.10 R01324 C TU_oxdhA1B_dsa_lpdA; 4 subunits likely to form a 2-oxoacid dehydrogenase complex; not pyruvate or 2-oxoglutarate 15556640 dh complex (lipoic acid absent in H. salinarum pyruvate and 2-oxoglutarate synthase); 2-oxoacid dehydrogenase 6266826 complex might be involved in branched-chain amino acid degradation as in T. acidophilum; 5780095 9827332 enz. purified, enz_act measured and inactivation investig.; pos_enz_activ; NMR; 13C NMR studies with labeled pyruvate fully consistent with active TCA cycle; pos_enz_activ; NMR; enz. complex with 2 subunits proven; cat. cycle of the enzyme invest.; also found in bact., e.g. H. pylori; 13C NMR studies with labeled pyruvate fully consistent with active TCA cycle; NO possible - compon. of EC 2.3.3.8; Acetyl-CoA + Citrate <=> Acetate + (3S)-Citryl-CoA NO possible - compon. of EC 4.1.3.6; 4.2.1.3 Citrate <=> Isocitrate YES secure OE4613F 5780095 9827332 pos_enz_activ; NMR; 13C NMR studies with labeled pyruvate fully consistent with active TCA cycle; R01325 C 4.2.1.3 Citrate <=> cis-Aconitate + H2O YES secure OE4613F R01899 C 1.1.1.42 Isocitrate + NADP+ <=> Oxalosuccinate + NADPH + H+ YES secure OE3634F R01900 C 4.2.1.3 Isocitrate <=> cis-Aconitate + H2O YES secure OE4613F R02164 C 1.3.5.1 Ubiquinone + Succinate <=> Ubiquinol + Fumarate YES OE2865R 4004256 insecure OE2866R 5780095 pos_enz_activ; NMR; enz. complex with 4 subunits pred.; 13C NMR studies with labeled pyruvate fully consistent with active TCA cycle; 10 OE2867R 9827332 OE2868R R02570 C 2.3.1.61 Succinyl-CoA + Dihydrolipoamide <=> CoA + SSuccinyldihydrolipoamide R03316 C 1.2.4.2 3-Carboxy-1-hydroxypropyl-ThPP + Lipoamide <=> NO S-Succinyldihydrolipoamide + unlikely Thiamin diphosphate R04450 C Citrate (pro-3S)-lyase (acetyl form) + H2O <=> NO 3.1.2.16 Citrate (pro-3S)-lyase (thiol form) unlikely + Acetate haloarchaea are the only archaea with a dihydrolipoamide S-acyltransferase (EC 2.3.1.-), which is likely to function in 15556640 reactions of a 2-oxoacid dehydrogenase complex (TU_oxdhA1B_dsa_lpdA); not part of pyruvate (EC 2.3.1.12) or 26266826 oxoglutarate (EC 2.3.1.61) dehydrogenase complex; NO unlikely TU_oxdhA1B_dsa_lpdA; 4 subunits likely to form a 2-oxoacid dehydrogenase complex; not pyruvate or 2-oxoglutarate 15556640 dh complex (lipoic acid absent in H. salinarum pyruvate and 2-oxoglutarate synthase); 2-oxoacid dehydrogenase 6266826 complex might be involved in branched-chain amino acid degradation as in T. acidophilum; 5 Nucleotide Metabolism De novo synthesis of purines react_id subsystem EC-No reaction status genes references comment R01049 P 2.7.6.1 ATP + D-Ribose 5-phosphate <=> AMP + 5-Phospho-alpha-D-ribose 1diphosphate YES OE4085R secure R01072 P 5-Phosphoribosylamine + Pyrophosphate + LGlutamate <=> 2.4.2.14 L-Glutamine + 5-Phospho-alpha-D-ribose 1diphosphate + H2O YES OE3139R secure R01083 P 4.3.2.2 N6-(1,2-Dicarboxyethyl)-AMP <=> Fumarate + AMP YES OE1623F secure R01127 P IMP + H2O <=> 3.5.4.10 1-(5'-Phosphoribosyl)-5-formamido-4imidazolecarboxamide archaeal type of IMP cyclohydrolase (EC 3.5.4.10); validated for PURO_METJA; unusual domain fusion of YES EC 2.1.2.2 and EC 2.1.2.3 in Hasal and Napha; in other org usually EC 3.5.4.10 fused with EC 2.1.2.3; OE4329F 11844782 secure bacterial IMP cyclohydrolase domain missing in archaea; instead this non-orthologous archaeal type of IMP cyclohydrolase; R04144 P ATP + 5-Phosphoribosylamine + Glycine <=> 6.3.4.13 ADP + Orthophosphate + 5'Phosphoribosylglycinamide YES OE2864F secure R04208 P 6.3.3.1 R04209 P 4.1.1.21 1-(5-Phospho-D-ribosyl)-5-amino-4- ATP + 2-(Formamido)-N1-(5'phosphoribosyl)acetamidine <=> ADP + Orthophosphate + Aminoimidazole ribotide YES OE2292F secure YES OE1951F 11 imidazolecarboxylate <=> Aminoimidazole ribotide + CO2 secure OE1952F R04325 P 2.1.2.2 10-Formyltetrahydrofolate + 5'Phosphoribosylglycinamide <=> Tetrahydrofolate + 5'-Phosphoribosyl-Nformylglycinamide YES OE1620R secure R04326 P 2.1.2.2 5'-Phosphoribosylglycinamide + 5,10Methenyltetrahydrofolate + H2O <=> 5'-Phosphoribosyl-N-formylglycinamide + Tetrahydrofolate YES OE1620R secure 6.3.5.3 ATP + 5'-Phosphoribosyl-Nformylglycinamide + L-Glutamine + H2O <=> YES OE2274R ADP + Orthophosphate + 2-(Formamido)-N1- secure OE3731R (5'-phosphoribosyl)acetamidine + L-Glutamate 4.3.2.2 1-(5'-Phosphoribosyl)-5-amino-4-(Nsuccinocarboxamide)-imidazole <=> Fumarate + 1-(5'-Phosphoribosyl)-5-amino-4imidazolecarboxamide YES OE1623F secure 2.1.2.3 10-Formyltetrahydrofolate + 1-(5'Phosphoribosyl)-5-amino-4imidazolecarboxamide <=> Tetrahydrofolate + 1-(5'-Phosphoribosyl)-5formamido-4-imidazolecarboxamide YES OE1620R secure 6.3.2.6 ATP + 1-(5-Phospho-D-ribosyl)-5-amino-4imidazolecarboxylate + L-Aspartate <=> ADP + Orthophosphate + 1-(5'Phosphoribosyl)-5-amino-4-(Nsuccinocarboxamide)-imidazole YES OE3724F secure R04463 P R04559 P R04560 P R04591 P De novo synthesis of pyrimidines react_id subsystem EC-No reaction status genes R00149 P 2 ATP + NH3 + CO2 + H2O <=> 6.3.4.16 2 ADP + Orthophosphate + Carbamoyl phosphate YES OE3554F secure OE3556R R00158 P 2.7.4.14 ATP + UMP <=> 2.7.4.22 ADP + UDP YES OE3429F secure R00571 P 6.3.4.2 ATP + UTP + NH3 <=> YES OE3572R ADP + Orthophosphate + CTP secure R00573 P 6.3.4.2 ATP + UTP + L-Glutamine + H2O <=> references comment YES OE3572R secure 12 ADP + Orthophosphate + CTP + L-Glutamate R00575 P 6.3.5.5 2 ATP + L-Glutamine + HCO3- + H2O <=> 2 ADP + Orthophosphate + LGlutamate + Carbamoyl phosphate R00965 P 4.1.1.23 Orotidine 5'-phosphate <=> UMP + CO2 YES a spontaneous 5-FOA-resistant mutant was found to contain an insertion in ura3 (OE3363F) and was a uracil auxotroph; OE3363F 10672188 secure integration of ura3 at the bacterioopsinlocus (bop) of this mutant restored 5-FOA sensitivity and uracil prototrophy; R01397 P 2.1.3.2 Carbamoyl phosphate + LAspartate <=> Orthophosphate + NCarbamoyl-L-aspartate YES OE5201F secure OE5202F R01867 P 1.3.3.1 (S)-Dihydroorotate + Oxygen <=> Orotate + H2O2 YES OE4508R secure R01870 P Orotidine 5'-phosphate + Pyrophosphate <=> 2.4.2.10 Orotate + 5-Phospho-alpha-Dribose 1-diphosphate R01993 P 3.5.2.3 YES OE3554F secure OE3556R OE3953R (pyrE2) is the likely orotate phosphoribosyltransferase, since the homolog from Haloferax volcanii has been shown to be functional; OE1672F (pyrE1) is similar to orotate phosphoribosyltransferases, but the homolog from Haloferax volcanii has been shown to be nonfunctional (Moshe Mevarech, personal communication); YES OE3953R secure (S)-Dihydroorotate + H2O <=> YES OE4558R N-Carbamoyl-L-aspartate secure Purine metabolism react_id subsystem EC-No reaction status genes R00024 C 4.1.1.39 D-Ribulose 1,5-bisphosphate + CO2 + H2O <=> 2 3-Phospho-D-glycerate R00124 P 2.7.4.6 ATP + ADP <=> ADP + ATP YES secure OE2667F R00127 P 2.7.4.3 ATP + AMP <=> 2 ADP YES secure OE3425F R00190 P 2.4.2.7 AMP + Pyrophosphate <=> Adenine + 5-Phospho-alpha-D-ribose 1diphosphate YES likely OE3951R OE1840R R00330 P 2.7.4.6 ATP + GDP <=> ADP + GTP YES secure OE2667F R00332 P 2.7.4.8 ATP + GMP <=> ADP + GDP YES insecure R01130 P 1.1.1.205 IMP + NAD+ + H2O <=> NO unlikely YES references comment 3255682 negative enzyme activity; reaction of novel archaeal AMP recycling pathway; no homolog to N. pharaonis 17303759 RuBisCO (NP2770A); - no guanylate kinase (EC 2.7.4.8) found, but adenylate kinase (EC 2.7.4.3, OE3425F); OE2458R 13 Xanthosine 5'-phosphate + NADH + H+ secure YES secure OE2579F OE2667F R01135 P 6.3.4.4 GTP + IMP + L-Aspartate <=> GDP + Orthophosphate + N6-(1,2Dicarboxyethyl)-AMP R01137 P 2.7.4.6 ATP + dADP <=> ADP + dATP YES secure R01230 P 6.3.4.1 ATP + Xanthosine 5'-phosphate + NH3 <=> AMP + Pyrophosphate + GMP YES OE1363F insecure OE3571R R01231 P 6.3.5.2 ATP + Xanthosine 5'-phosphate + LGlutamine + H2O <=> AMP + Pyrophosphate + GMP + LGlutamate YES secure OE1363F OE3571R R01857 P 2.7.4.6 ATP + dGDP <=> ADP + dGTP YES secure OE2667F R02014 P 1.17.4.2 dATP + Oxidized thioredoxin + H2O <=> ATP + Thioredoxin NO unlikely R02017 P 1.17.4.1 dADP + Oxidized thioredoxin + H2O <=> Thioredoxin + ADP R02019 P 1.17.4.1 R02020 P - cobalamine-dep. ribonucleoside-P2 reductase (EC 1.17.4.1) in Hasal, not ribonucleotide-P3 reductase (EC 1.17.4.2); YES secure OE4345R OE4346R cobalamine-dep. ribonucleoside-P2 reductase (EC 1.17.4.1) in Hasal, not ribonucleotide-P3 reductase (EC 1.17.4.2); dGDP + Oxidized thioredoxin + H2O <=> GDP + Thioredoxin YES secure OE4345R OE4346R cobalamine-dep. ribonucleoside-P2 reductase (EC 1.17.4.1) in Hasal, not ribonucleotide-P3 reductase (EC 1.17.4.2); 1.17.4.2 dGTP + Oxidized thioredoxin + H2O <=> GTP + Thioredoxin NO unlikely - cobalamine-dep. ribonucleoside-P2 reductase (EC 1.17.4.1) in Hasal, not ribonucleotide-P3 reductase (EC 1.17.4.2); R10009 P - AMP + Orthophosphate <=> D-Ribose 1,5-bisphosphate + Adenine NO unlikely 17303759 reaction of novel archaeal AMP recycling pathway; no homolog to N. pharaonis AMP phosphorylase (NP3958A); R10010 P - D-Ribose 1,5-bisphosphate <=> D-Ribulose 1,5-bisphosphate YES likely OE3610R 17303759 reaction of novel archaeal AMP recycling pathway; all pathway enzymes encoded by N. pharaonis, but only ribose-1,5-biphosphate isomerase encoded by H. salinarum; Pyrimidine metabolism react_id subsystem EC-No reaction status genes R00156 P 2.7.4.6 ATP + UDP <=> ADP + UTP YES secure OE2667F R00568 P 3.5.4.13 CTP + H2O <=> UTP + NH3 YES secure OE1384F R00570 P 2.7.4.6 ATP + CDP <=> ADP + CTP YES secure OE2667F R00964 P 2.7.1.48 ATP + Uridine <=> ADP + UMP YES secure OE3159R references comment 14 R00966 P 2.4.2.9 UMP + Pyrophosphate <=> Uracil + 5-Phospho-alpha-D-ribose 1diphosphate YES secure OE4234R R01567 P 2.7.1.21 ATP + Thymidine <=> ADP + dTMP YES secure OE3159R R02016 P 1.8.1.9 Thioredoxin + NADP+ <=> Oxidized thioredoxin + NADPH + H+ YES secure OE2805R R02018 P 1.17.4.1 dUDP + Oxidized thioredoxin + H2O <=> Thioredoxin + UDP YES secure OE4345R OE4346R R02022 P 1.17.4.2 dCTP + Oxidized thioredoxin + H2O <=> CTP + Thioredoxin NO unlikely - cobalamine-dep. ribonucleoside-P2 reductase (EC 1.17.4.1) in Hasal, not ribonucleotide-P3 reductase (EC 1.17.4.2); R02023 P 1.17.4.2 dUTP + Oxidized thioredoxin + H2O <=> UTP + Thioredoxin NO unlikely - cobalamine-dep. ribonucleoside-P2 reductase (EC 1.17.4.1) in Hasal, not ribonucleotide-P3 reductase (EC 1.17.4.2); R02024 P 1.17.4.1 dCDP + Oxidized thioredoxin + H2O <=> Thioredoxin + CDP YES secure OE4345R OE4346R cobalamine-dep. ribonucleoside-P2 reductase (EC 1.17.4.1) in Hasal, not ribonucleotide-P3 reductase (EC 1.17.4.2); R02093 P 2.7.4.6 ATP + dTDP <=> ADP + dTTP YES secure OE2667F R02094 P 2.7.4.9 ATP + dTMP <=> ADP + dTDP YES secure OE3715R R02098 P 2.7.4.9 ATP + dUMP <=> ADP + dUDP YES secure OE3715R R02101 P 2.1.1.45 dUMP + 5,10-Methylenetetrahydrofolate <=> Dihydrofolate + dTMP NO unlikely R02325 P 3.5.4.13 dCTP + H2O <=> dUTP + NH3 YES secure OE1384F R02326 P 2.7.4.6 ATP + dCDP <=> ADP + dCTP YES secure OE2667F R02331 P 2.7.4.6 ATP + dUDP <=> ADP + dUTP R06613 P 5,10-Methylenetetrahydrofolate + dUMP + 2.1.1.148 FADH2 <=> Tetrahydrofolate + dTMP + FAD cobalamine-dep. ribonucleoside-P2 reductase (EC 1.17.4.1) in Hasal, not ribonucleotide-P3 reductase (EC 1.17.4.2); - folate-dependent thimidylate kinase (EC 2.1.1.45, thyA) in Napha and Hqwal; non-orthologous flavindependent thimidylate kinase (EC 2.1.1.148, thyX) in Hasal and Hamar; YES secure OE2667F YES secure OE2898R - folate-dependent thimidylate kinase (EC 2.1.1.45, thyA) in Napha and Hqwal; non-orthologous flavindependent thimidylate kinase (EC 2.1.1.148, thyX) in Hasal and Hamar; 15 6 Lipid metabolism Mevalonate pathway react_id subsystem EC-No reaction status genes references comment NMR; radiolabelling; first step of mevalonate pathway modified since one two-carbon fragment of mevalonate not derived from acetate, but from an aa (Lys); phytanyl chains derived via mevalonate; acetate, pyruvate, glycerol, lysine, and further aa incorporated into phytanyl chains; R00238 L 2.3.1.9 2 Acetyl-CoA <=> 2.3.1.16 CoA + Acetoacetyl-CoA YES OE3884F 3700337 insecure R01121 L ATP + (R)-5Diphosphomevalonate <=> 4.1.1.33 ADP + Orthophosphate + Isopentenyl diphosphate + CO2 YES secure OE1893F R01123 L 5.3.3.2 Isopentenyl diphosphate <=> Dimethylallyl diphosphate YES secure OE3560F OE6213R 3700337 OE7093R R01978 L 2.3.3.10 (S)-3-Hydroxy-3-methylglutarylCoA + CoA <=> YES Acetyl-CoA + H2O + secure Acetoacetyl-CoA OE3296F archaea: mevalonate-P => isopentenyl-P => isopentenyl-P2; bacteria: mevalonate-P => mevalonate-P2 => isopentenyl3700337 P2; haloarchaea possess archaeal-type kinase but bacterial-type decarboxylase; genetic evidence for bacterial 16621811 decarboxylase step (OE1893F) and archaeal kinase step (OE2647F); R02082 L 1.1.1.34 (R)-Mevalonate + CoA + 2 NADP+ <=> YES (S)-3-Hydroxy-3-methylglutaryl- secure CoA + 2 NADPH OE3637R archaea: mevalonate-P => isopentenyl-P => isopentenyl-P2; bacteria: mevalonate-P => mevalonate-P2 => isopentenyl3700337 P2; haloarchaea possess archaeal-type kinase but bacterial-type decarboxylase; genetic evidence for bacterial 16621811 decarboxylase step (OE1893F) and archaeal kinase step (OE2647F); R02245 L 2.7.1.36 ATP + (R)-Mevalonate <=> YES ADP + (R)-5-Phosphomevalonate secure OE2645F archaea: mevalonate-P => isopentenyl-P => isopentenyl-P2; bacteria: mevalonate-P => mevalonate-P2 => isopentenyl3700337 P2; haloarchaea possess archaeal-type kinase but bacterial-type decarboxylase; genetic evidence for bacterial 16621811 decarboxylase step (OE1893F) and archaeal kinase step (OE2647F); 2.7.4.2 ATP + (R)-5-Phosphomevalonate archaea: mevalonate-P => isopentenyl-P => isopentenyl-P2; bacteria: mevalonate-P => mevalonate-P2 => isopentenyl<=> YES 3700337 OE2647F P2; haloarchaea possess archaeal-type kinase but bacterial-type decarboxylase; genetic evidence for bacterial ADP + (R)-5insecure 16621811 decarboxylase step (OE1893F) and archaeal kinase step (OE2647F); Diphosphomevalonate R03245 L archaea: mevalonate-P => isopentenyl-P => isopentenyl-P2; bacteria: mevalonate-P => mevalonate-P2 => isopentenyl3700337 P2; haloarchaea possess archaeal-type kinase but bacterial-type decarboxylase; genetic evidence for bacterial 16621811 decarboxylase step (OE1893F) and archaeal kinase step (OE2647F); archaeal (OE6213R,OE7093R, plasmid) and bacterial (OE3560F, chromosome) type of IPP isomerase in Hasal; NMR; radiolabelling; phytanyl chains derived via mevalonate; acetate, pyruvate, glycerol, lysine, and further aa incorporated into phytanyl chains; unusual labelling pattern indicate modified mevalonate pathway; De novo synthesis of isoprenoids react_id subsystem EC-No reaction status genes references comment R00702 L 2 trans,trans-Farnesyl diphosphate <=> 2.5.1.21 Pyrophosphate + Presqualene diphosphate + H+ YES likely OE2014F 2857171 R01658 L 2.5.1.1 2.5.1.10 2.5.1.29 2.5.1.- Dimethylallyl diphosphate + Isopentenyl diphosphate <=> Pyrophosphate + Geranyl diphosphate YES secure archaea: mevalonate-P => isopentenyl-P => isopentenyl-P2; bacteria: mevalonate-P => mevalonate-P2 => OE2650F 3700337 isopentenyl-P2; haloarchaea possess archaeal-type kinase but bacterial-type decarboxylase; genetic evidence for OE4010F 16621811 bacterial decarboxylase step (OE1893F) and archaeal kinase step (OE2647F); R02003 L 2.5.1.1 Geranyl diphosphate + Isopentenyl YES OE2650F 3700337 several isoprenoids and derived compounds were identified in Halobacterium, e.g. menaquinone (C30-C45), dolichol (C60), squalene (C30), and phytoene (C40); archaea: mevalonate-P => isopentenyl-P => isopentenyl-P2; bacteria: mevalonate-P => mevalonate-P2 => 16 2.5.1.10 diphosphate <=> secure 2.5.1.29 Pyrophosphate + trans,trans-Farnesyl 2.5.1.- diphosphate OE4010F 16621811 isopentenyl-P2; haloarchaea possess archaeal-type kinase but bacterial-type decarboxylase; genetic evidence for bacterial decarboxylase step (OE1893F) and archaeal kinase step (OE2647F); 2.5.1.1 2.5.1.10 2.5.1.29 2.5.1.- trans,trans-Farnesyl diphosphate + Isopentenyl diphosphate <=> Pyrophosphate + Geranylgeranyl diphosphate YES secure R02063 L 1.3.1.- Geranylgeranyl diphosphate + H+ + 3 NADPH <=> Phytyl diphosphate + 3 NADP+ OE1657R archaea: mevalonate-P => isopentenyl-P => isopentenyl-P2; bacteria: mevalonate-P => mevalonate-P2 => YES OE1699R 3700337 isopentenyl-P2; haloarchaea possess archaeal-type kinase but bacterial-type decarboxylase; genetic evidence for insecure OE2720R 16621811 bacterial decarboxylase step (OE1893F) and archaeal kinase step (OE2647F); OE4702F R02065 L 2 Geranylgeranyl diphosphate <=> 2.5.1.32 Pyrophosphate + Prephytoene diphosphate + H+ YES secure OE3093R 2857171 OE3376F several isoprenoids and derived compounds were identified in Halobacterium, e.g. menaquinone (C30-C45), dolichol (C60), squalene (C30), and phytoene (C40); R02872 L Presqualene diphosphate + NADPH YES 2.5.1.21 + H+ <=> likely Pyrophosphate + Squalene + NADP+ OE2014F 2857171 several isoprenoids and derived compounds were identified in Halobacterium, e.g. menaquinone (C30-C45), dolichol (C60), squalene (C30), and phytoene (C40); R05555 L trans,trans-Farnesyl diphosphate + 2.5.1.31 Isopentenyl diphosphate <=> 2.5.1.- trans,trans,cis-Geranylgeranyl diphosphate + Pyrophosphate YES secure OE3503F 2857171 several isoprenoids and derived compounds were identified in Halobacterium, e.g. menaquinone (C30-C45), dolichol (C60), squalene (C30), and phytoene (C40); R05611 L all-trans-Octaprenyl diphosphate + 2.5.1.11 Isopentenyl diphosphate <=> 2.5.1.- all-trans-Heptaprenyl diphosphate + Pyrophosphate YES secure OE2650F 2857171 OE4010F several isoprenoids and derived compounds were identified in Halobacterium, e.g. menaquinone (C30-C45), dolichol (C60), squalene (C30), and phytoene (C40); R05612 L all-trans-Hexaprenyl diphosphate + Isopentenyl diphosphate <=> 2.5.1.30 all-trans-Heptaprenyl diphosphate + Pyrophosphate YES secure OE2650F 2857171 OE4010F several isoprenoids and derived compounds were identified in Halobacterium, e.g. menaquinone (C30-C45), dolichol (C60), squalene (C30), and phytoene (C40); R05613 L all-trans-Pentaprenyl diphosphate + Isopentenyl diphosphate <=> 2.5.1.33 all-trans-Hexaprenyl diphosphate + Pyrophosphate YES secure OE2650F 2857171 OE4010F several isoprenoids and derived compounds were identified in Halobacterium, e.g. menaquinone (C30-C45), dolichol (C60), squalene (C30), and phytoene (C40); R06447 L trans,trans,cis-Geranylgeranyl diphosphate + 7 Isopentenyl 2.5.1.31 diphosphate <=> 2.5.1.di-trans,poly-cis-Undecaprenyl diphosphate + 7 Pyrophosphate YES secure OE3503F 2857171 several isoprenoids and derived compounds were identified in Halobacterium, e.g. menaquinone (C30-C45), dolichol (C60), squalene (C30), and phytoene (C40); YES secure OE2650F 2857171 OE4010F several isoprenoids and derived compounds were identified in Halobacterium, e.g. menaquinone (C30-C45), dolichol (C60), squalene (C30), and phytoene (C40); YES OE2650F 2857171 several isoprenoids and derived compounds were identified in Halobacterium, e.g. menaquinone (C30-C45), dolichol R02061 L Geranylgeranyl diphosphate + Isopentenyl diphosphate <=> all-trans-Pentaprenyl diphosphate + Pyrophosphate R10003 L 2.5.1.- R10004 L 2.5.1.11 all-trans-Octaprenyl diphosphate + archaea: mevalonate-P => isopentenyl-P => isopentenyl-P2; bacteria: mevalonate-P => mevalonate-P2 => OE2650F 3700337 isopentenyl-P2; haloarchaea possess archaeal-type kinase but bacterial-type decarboxylase; genetic evidence for OE4010F 16621811 bacterial decarboxylase step (OE1893F) and archaeal kinase step (OE2647F); 17 Isopentenyl diphosphate <=> all-trans-Nonaprenyl diphosphate + Pyrophosphate R10005 L secure Prephytoene diphosphate + H+ + YES 2.5.1.32 NADPH <=> secure Pyrophosphate + Phytoene + NADP+ OE4010F (C60), squalene (C30), and phytoene (C40); OE3093R 2857171 OE3376F several isoprenoids and derived compounds were identified in Halobacterium, e.g. menaquinone (C30-C45), dolichol (C60), squalene (C30), and phytoene (C40); Synthesis of carotenoids and retinal react_id subsystem R00032 L EC-No reaction beta-Carotene + 1.14.99.36 Oxygen <=> 2 Retinal status genes YES insecure references comment step required since retinal proteins exist in H. salinarum; no homologue to other beta-carotene 15,15'-dioxygenases found yet; H. walsbyi encodes two cyanobacterial-like (HQ2381A, HQ2020A) and one plant-like &Â carotene mono-oxygenase homologs 11092896 (HQ3007A) (PMID: 16820047); decrease of retinal/ increase of beta-carotene levels by deletion of OE3102R (brp) and OE3980R 11226271 (blh) (PMID:11092896); brp or blh may regulate or catalyze the oxidative cleavage of beta-carotene; brp and blh show no simil. 16820047 to eukaryotic beta-carotene 15,15'-dioxygenases (PMID:11092896, PMID:11226271); blh (OE3980R) located next to lycopene cyclase (OE3983R) in haloarchael genomes; brp (OE3102R) located next to bop (OE3102R); 2.5.1.32 2 Geranylgeranyl diphosphate <=> Pyrophosphate + Prephytoene diphosphate + H+ YES secure OE3093R 2857171 OE3376F R03823 L 1.14.-.- beta-Carotene + Acceptor <=> Lycopene + Reduced acceptor YES secure OE3983R 12003928 knock-out mutants accumulated lycopene; probable TU_crtY_blh; close to trans-prenyltransferase (idsA2); R04786 L 1.14.99.- Phytoene <=> Phytofluene + Hydrogen YES secure OE3381R OE3468R phytoene desaturase (crtI, OE3381R and OE3468R) might catalyze up to four consecutive desaturation steps from phytoene to lycopene; carotene 7,8-desaturase (crtQ) unlikely in Hasal; R04787 L 1.14.99.- Phytofluene <=> zeta-Carotene YES secure OE3381R OE3468R phytoene desaturase (crtI, OE3381R and OE3468R) might catalyze up to four consecutive desaturation steps from phytoene to lycopene; carotene 7,8-desaturase (crtQ) unlikely in Hasal; R04798 L 1.14.99.- zeta-Carotene <=> Neurosporene + Hydrogen YES secure OE3381R OE3468R phytoene desaturase (crtI, OE3381R and OE3468R) might catalyze up to four consecutive desaturation steps from phytoene to lycopene; carotene 7,8-desaturase (crtQ) unlikely in Hasal; R04799 L zeta-Carotene + 1.14.99.- Acceptor <=> 1.14.99.30 Lycopene + Reduced acceptor YES secure OE3381R OE3468R phytoene desaturase (crtI, OE3381R and OE3468R) might catalyze up to four consecutive desaturation steps from phytoene to lycopene; carotene 7,8-desaturase (crtQ) unlikely in Hasal; R04800 L Neurosporene + Reduced acceptor + Oxygen <=> Lycopene + Acceptor + 2 H2O YES secure OE3381R OE3468R phytoene desaturase (crtI, OE3381R and OE3468R) might catalyze up to four consecutive desaturation steps from phytoene to lycopene; carotene 7,8-desaturase (crtQ) unlikely in Hasal; R02065 L 1.14.99.- several isoprenoids and derived compounds were identified in Halobacterium, e.g. menaquinone (C30-C45), dolichol (C60), squalene (C30), and phytoene (C40); 18 R10005 L 2.5.1.32 Prephytoene diphosphate + H+ + NADPH <=> Pyrophosphate + Phytoene + NADP+ YES secure OE3093R 2857171 OE3376F several isoprenoids and derived compounds were identified in Halobacterium, e.g. menaquinone (C30-C45), dolichol (C60), squalene (C30), and phytoene (C40); Fatty acid metabolism react_id subsystem EC-No reaction R00238 L 2.3.1.9 2 Acetyl-CoA <=> 2.3.1.16 CoA + Acetoacetyl-CoA R00391 L 2.3.1.16 Acyl-CoA + Acetyl-CoA <=> CoA + 3-Oxoacyl-CoA status genes references YES OE3884F 3700337 insecure YES secure OE3884F R00392 L 1.3.99.3 Acyl-CoA + Acceptor <=> 2,3-Dehydroacyl-CoA + Reduced acceptor YES secure OE1555F OE2013R OE2138F OE2710F OE3123R OE4500R R00829 L 2.3.1.16 Succinyl-CoA + Acetyl-CoA <=> CoA + 3-Oxoadipyl-CoA YES secure OE3884F R00833 L 5.4.99.2 (R)-2-Methyl-3-oxopropanoyl-CoA <=> Succinyl-CoA YES secure OE1721R OE1972F OE2005F R00924 L 1.3.99.3 Propanoyl-CoA + FAD <=> FADH2 + Propenoyl-CoA YES secure OE1555F OE2013R OE2138F OE2710F OE3123R OE4500R R00927 L 2.3.1.16 Propanoyl-CoA + Acetyl-CoA <=> CoA + 2-Methylacetoacetyl-CoA YES secure OE3884F R01175 L 1.3.99.3 Butanoyl-CoA + FAD <=> FADH2 + Crotonoyl-CoA YES secure OE1555F OE2013R OE2138F OE2710F OE3123R OE4500R R01177 L 2.3.1.16 Acetyl-CoA + Butanoyl-CoA <=> CoA + 3-Oxohexanoyl-CoA YES secure OE3884F R01279 L 1.3.99.3 Palmitoyl-CoA + FAD <=> YES OE1555F comment NMR; radiolabelling; first step of mevalonate pathway modified since one two-carbon fragment of mevalonate not derived from acetate, but from an aa (Lys); phytanyl chains derived via mevalonate; acetate, pyruvate, glycerol, lysine, and further aa incorporated into phytanyl chains; all enzyme genes for methylmalonyl metabolism found; several paralogs available for most steps; 19 trans-Hexadec-2-enoyl-CoA + FADH2 secure OE2013R OE2138F OE2710F OE3123R OE4500R R01778 L 1.1.1.35 (3S)-3-Hydroxyacyl-CoA + NAD+ <=> 3-Oxoacyl-CoA + NADH YES secure OE2015R OE2871F OE3846R R01859 L 6.4.1.3 ATP + Propanoyl-CoA + HCO3- <=> ADP + Orthophosphate + (S)-2-Methyl-3oxopropanoyl-CoA YES secure OE1939F OE3175F OE3177F R01975 L 1.1.1.35 (S)-3-Hydroxybutanoyl-CoA + NAD+ <=> Acetoacetyl-CoA + NADH YES secure OE2015R OE2871F OE3846R R02661 L 1.3.99.3 2-Methylpropanoyl-CoA + FAD <=> 2-Methylprop-2-enoyl-CoA + FADH2 YES secure OE1555F OE2013R OE2138F OE2710F OE3123R OE4500R R02685 L 4.2.1.17 (3S)-3-Hydroxyacyl-CoA <=> trans-2,3-Dehydroacyl-CoA + H2O YES secure OE1641R OE3846R R02765 L 5.1.99.1 (R)-2-Methyl-3-oxopropanoyl-CoA <=> (S)-2-Methyl-3-oxopropanoyl-CoA YES likely OE1718R OE1899R OE2610F R03026 L 4.2.1.17 (S)-3-Hydroxybutanoyl-CoA <=> Crotonoyl-CoA + H2O YES secure OE1641R OE3846R R03045 L 4.2.1.17 3-Hydroxypropionyl-CoA <=> Propenoyl-CoA + H2O YES secure OE1641R OE3846R R03172 L 1.3.99.3 2-Methylbutanoyl-CoA + FAD <=> 2-Methylbut-2-enoyl-CoA + FADH2 YES secure OE1555F OE2013R OE2138F OE2710F OE3123R OE4500R R03224 L 4.2.1.17 (3R)-3-Hydroxyacyl-CoA <=> cis-2,3-Dehydroacyl-CoA + H2O YES secure OE1641R OE3846R R03719 L Propanoyl-CoA + Choloyl-CoA <=> 2.3.1.16 CoA + 3alpha,7alpha,12alpha-Trihydroxy5beta-24-oxocholestanoyl-CoA YES secure OE3884F R03777 L 1.3.99.3 Octanoyl-CoA + FAD <=> trans-Oct-2-enoyl-CoA + FADH2 YES secure OE1555F OE2013R propionyl-CoA carboxylase subunits are encoded within fatty-acid degradation cluster and next to biotin synthesis cluster in N. pharaonis; all enzyme genes for methylmalonyl metabolism found; several paralogs available for most steps; 20 OE2138F OE2710F OE3123R OE4500R R03778 L 2.3.1.16 Octanoyl-CoA + Acetyl-CoA <=> CoA + 3-Oxodecanoyl-CoA YES secure OE3884F R03857 L 1.3.99.3 Lauroyl-CoA + FAD <=> 2-trans-Dodecenoyl-CoA + FADH2 YES secure OE1555F OE2013R OE2138F OE2710F OE3123R OE4500R R03858 L 2.3.1.16 Lauroyl-CoA + Acetyl-CoA <=> CoA + 3-Oxotetradecanoyl-CoA YES secure OE3884F R03990 L 1.3.99.3 Tetradecanoyl-CoA + FAD <=> trans-Tetradec-2-enoyl-CoA + FADH2 YES secure OE1555F OE2013R OE2138F OE2710F OE3123R OE4500R R03991 L 2.3.1.16 Tetradecanoyl-CoA + Acetyl-CoA <=> CoA + 3-Oxopalmitoyl-CoA YES secure OE3884F R04095 L 1.3.99.3 3-Methylbutanoyl-CoA + FAD <=> 3-Methylcrotonyl-CoA + FADH2 YES secure OE1555F OE2013R OE2138F OE2710F OE3123R OE4500R R04137 L 4.2.1.17 3-Hydroxyisovaleryl-CoA <=> 3-Methylcrotonyl-CoA + H2O YES secure OE1641R OE3846R R04170 L 4.2.1.17 (S)-3-Hydroxydodecanoyl-CoA <=> 2-trans-Dodecenoyl-CoA + H2O YES secure OE1641R OE3846R R04203 L (2S,3S)-3-Hydroxy-2-methylbutanoyl-CoA + 1.1.1.35 NAD+ <=> 2-Methylacetoacetyl-CoA + NADH YES secure OE2015R OE2871F OE3846R R04204 L (2S,3S)-3-Hydroxy-2-methylbutanoyl-CoA 4.2.1.17 <=> 2-Methylbut-2-enoyl-CoA + H2O YES secure OE1641R OE3846R R04224 L 4.2.1.17 2-Methylprop-2-enoyl-CoA + H2O <=> (S)-3-Hydroxyisobutyryl-CoA YES secure OE1641R OE3846R R04432 L 1.3.99.3 Electron-transferring flavoprotein + Propanoyl- YES CoA <=> secure OE1555F OE2013R 21 Reduced electron-transferring flavoprotein + Propenoyl-CoA OE2138F OE2710F OE3123R OE4500R R04546 L Propanoyl-CoA + Chenodeoxycholoyl-CoA <=> 2.3.1.16 CoA + 3alpha,7alpha-Dihydroxy-5betacholestanoyl-CoA YES secure OE3884F R04737 L (S)-3-Hydroxyhexadecanoyl-CoA + NAD+ 1.1.1.35 <=> 3-Oxopalmitoyl-CoA + NADH YES secure OE2015R OE2871F OE3846R R04738 L 4.2.1.17 YES secure OE1641R OE3846R R04739 L (S)-3-Hydroxytetradecanoyl-CoA + NAD+ 1.1.1.35 <=> 3-Oxotetradecanoyl-CoA + NADH YES secure OE2015R OE2871F OE3846R R04740 L 4.2.1.17 (S)-3-Hydroxytetradecanoyl-CoA <=> trans-Tetradec-2-enoyl-CoA + H2O YES secure OE1641R OE3846R R04741 L 1.1.1.35 (S)-3-Hydroxydodecanoyl-CoA + NAD+ <=> 3-Oxododecanoyl-CoA + NADH YES secure OE2015R OE2871F OE3846R R04742 L 2.3.1.16 Decanoyl-CoA + Acetyl-CoA <=> CoA + 3-Oxododecanoyl-CoA YES secure OE3884F R04743 L 1.1.1.35 (S)-Hydroxydecanoyl-CoA + NAD+ <=> 3-Oxodecanoyl-CoA + NADH YES secure OE2015R OE2871F OE3846R R04744 L 4.2.1.17 (S)-Hydroxydecanoyl-CoA <=> trans-Dec-2-enoyl-CoA + H2O YES secure OE1641R OE3846R R04745 L 1.1.1.35 (S)-Hydroxyoctanoyl-CoA + NAD+ <=> 3-Oxooctanoyl-CoA + NADH YES secure OE2015R OE2871F OE3846R R04746 L 4.2.1.17 (S)-Hydroxyoctanoyl-CoA <=> trans-Oct-2-enoyl-CoA + H2O YES secure OE1641R OE3846R R04747 L 2.3.1.16 Hexanoyl-CoA + Acetyl-CoA <=> CoA + 3-Oxooctanoyl-CoA YES secure OE3884F R04748 L 1.1.1.35 (S)-Hydroxyhexanoyl-CoA + NAD+ <=> 3-Oxohexanoyl-CoA + NADH YES secure OE2015R OE2871F OE3846R R04749 L 4.2.1.17 (S)-Hydroxyhexanoyl-CoA <=> trans-Hex-2-enoyl-CoA + H2O YES secure OE1641R OE3846R R04751 L 1.3.99.3 Hexanoyl-CoA + FAD <=> YES OE1555F (S)-3-Hydroxyhexadecanoyl-CoA <=> trans-Hexadec-2-enoyl-CoA + H2O 22 trans-Hex-2-enoyl-CoA + FADH2 secure OE2013R OE2138F OE2710F OE3123R OE4500R R04754 L 1.3.99.3 Decanoyl-CoA + FAD <=> trans-Dec-2-enoyl-CoA + FADH2 YES secure OE1555F OE2013R OE2138F OE2710F OE3123R OE4500R R04811 L Propanoyl-CoA + ChenodeoxyglycocholoylCoA <=> 2.3.1.16 CoA + 3alpha,7alpha-Dihydroxy-5beta-24oxocholestanoyl-CoA YES secure OE3884F R05066 L (S)-3-Hydroxyisobutyrate + NAD+ <=> 1.1.1.35 (S)-Methylmalonate semialdehyde + NADH + H+ YES secure OE2015R OE2871F OE3846R R05575 L (Hydroxymethylphenyl)succinyl-CoA + NAD+ YES 1.1.1.35 <=> secure Benzoylsuccinyl-CoA + NADH + H+ OE2015R OE2871F OE3846R R05595 L 4.2.1.17 R06411 L cis-2-Methyl-5-isopropylhexa-2,5-dienoylCoA + H2O <=> 4.2.1.17 3-Hydroxy-2,6-dimethyl-5-methyleneheptanoyl-CoA R06412 L 4.2.1.17 Crotonoyl-CoA + H2O <=> 3-Hydroxybutanoyl-CoA trans-2-Methyl-5-isopropylhexa-2,5-dienoylCoA + H2O <=> 3-Hydroxy-2,6-dimethyl-5-methyleneheptanoyl-CoA YES secure OE1641R OE3846R YES secure OE1641R OE3846R YES secure OE1641R OE3846R 23 7 Amino acid synthesis´ Glutamate family (glutamate, glutamine, proline, arginine) react_id subsystem EC-No reaction status genes references comment R00093 A 2 L-Glutamate + NAD+ <=> 1.4.1.14 L-Glutamine + 2Oxoglutarate + NADH NO unlikely - - reaction important for N-assimilation, e.g. in N. pharaonis; R00114 A 2 L-Glutamate + NADP+ <=> 1.4.1.13 L-Glutamine + 2Oxoglutarate + NADPH + H+ NO unlikely - - reaction important for N-assimilation, e.g. in N. pharaonis; R00239 A ATP + L-Glutamate <=> 2.7.2.11 ADP + L-Glutamyl 5phosphate NO unlikely - R00243 A 1.4.1.2 1.4.1.3 L-Glutamate + NAD+ + H2O <=> 2-Oxoglutarate + NH3 + NADH + H+ YES secure 2917175 3700337 8157586 OE1270F 8605224 OE2728R 9827332 10076069 12052548 pos_enz_activ; kinetic mechanism of a purified NAD+-dependent glutamate dehydrogenase (EC 1.4.1.2) was investigated (Bonete et al, Int. J. Biochem. 19, 1149-55 (1987), PMID:2917175 (1989), PMID:10076069 (1999), PMID:12052548 (2002)); inhibition and activation of this enzyme by TCA intermediates and amino acids was studied (PMID: 8605224 (1996)); halophilic enzymes (EC 1.4.1.2) only available archaeal seq; archaeal seq all assigned as EC 1.4.1.3; NMR; glutamate signals were detected from labeled pyruvate and alanine (PMID:8157586;PMID:9827332) as well as from acetate and glycerol (PMID: 3700337); R00245 A L-Glutamate 5semialdehyde + NAD+ + 1.5.1.12 H2O <=> L-Glutamate + NADH + H+ YES likely OE2133R OE2190R 9827332 OE2367F OE4529F NMR; proline signals were detected from labeled alanine; proline signals were also detected from labeled pyruvate in the presence of malonate (succinate dehydrogenase inhibitor) under anaerobic conditions; all gene candidates are aldehyde dehydrogenase homologs; R00248 A 1.4.1.3 1.4.1.4 L-Glutamate + NADP+ + H2O <=> 2-Oxoglutarate + NH3 + NADPH + H+ YES secure 1980084 3700337 OE1943F 8157586 OE2728R 9827332 12052548 pos_enz_activ; kinetic mechanism of a purified glutamate dehydrogenase from H. salinarum was investigated (PMID: Bonete et al, Int. J. Biochem. 19, 1149-55 (1987), PMID: 1980084 (1990), PMID: 12052548 (2002)); the enzyme shows activity with NADP+ as cofactor (EC 1.4.1.4), but NAD+ specifity was not tested (EC 1.4.1.3 cannot be excluded); halophilic enzymes (EC 1.4.1.4) only available archaeal seq; archaeal seq all assigned as EC 1.4.1.3; NMR; glutamate signals were detected from labeled pyruvate and alanine (PMID:8157586;PMID:9827332) as well as from acetate and glycerol (PMID: 3700337); R00253 A 6.3.1.2 ATP + L-Glutamate + NH3 <=> YES ADP + Orthophosphate + secure L-Glutamine OE3922R - Glu not required for protein synth; Glu loaded to tRNA amidotransf. and then amidated; R00256 A 3.5.1.2 L-Glutamine + H2O <=> 3.5.1.38 L-Glutamate + NH3 NO unlikely - - Glu not required for protein synth; Glu loaded to tRNA amidotransf. and then amidated; R00259 A 2.3.1.1 Acetyl-CoA + L-Glutamate NO <=> unlikely CoA + N-Acetyl-L- - - Arg is an essential aa in Hasal; no arg cluster found as in Napha; no homologs for both ornithine synthesis pathways; 24 glutamate NO questionable 15715981 OE1498R is homologous to novel archaeal Tyr decarboxylase; OE1498R was formerly a Glu decarboxylase candidate; R00667 A L-Ornithine + 2Oxoglutarate <=> 2.6.1.13 L-Glutamate 5semialdehyde + LGlutamate NO unlikely - - Arg is an essential aa in Hasal; no arg cluster found as in Napha; no homologs for both ornithine synthesis pathways; R00669 A N-Acetylornithine + H2O 3.5.1.14 <=> 3.5.1.16 Acetate + L-Ornithine NO unlikely - - Arg is an essential aa in Hasal; no arg cluster found as in Napha; no homologs for both ornithine synthesis pathways; R00671 - 4.3.1.12 L-Ornithine <=> L-Proline + NH3 YES insecure OE4121R OE2945F R00707 A (S)-1-Pyrroline-5carboxylate + NAD+ + 2 1.5.1.12 H2O <=> L-Glutamate + NADH + H+ YES likely OE2133R OE2190R 9827332 OE2367F OE4529F NMR; proline signals were detected from labeled alanine; proline signals were also detected from labeled pyruvate in the presence of malonate (succinate dehydrogenase inhibitor) under anaerobic conditions; all gene candidates are aldehyde dehydrogenase homologs; R00708 A (S)-1-Pyrroline-5carboxylate + NADP+ + 2 1.5.1.12 H2O <=> L-Glutamate + NADPH + H+ YES likely OE2133R OE2190R 9827332 OE2367F OE4529F NMR; proline signals were detected from labeled alanine; proline signals were also detected from labeled pyruvate in the presence of malonate (succinate dehydrogenase inhibitor) under anaerobic conditions; all gene candidates are aldehyde dehydrogenase homologs; R01248 A 1.5.1.2 L-Proline + NAD+ <=> NO (S)-1-Pyrroline-5unlikely carboxylate + NADH + H+ - - no hits with Methanobrevibacter smithii, S. solfataricus enzymes; R01251 A 1.5.1.2 L-Proline + NADP+ <=> (S)-1-Pyrroline-5carboxylate + NADPH + H+ NO unlikely - - no hits with Methanobrevibacter smithii, S. solfataricus enzymes; R01253 A L-Proline + Acceptor + H2O <=> 1.5.99.8 (S)-1-Pyrroline-5carboxylate + Reduced acceptor YES likely OE3955F 9827332 NMR; proline signals were detected from labeled alanine; proline signals were also detected from labeled pyruvate in the presence of malonate (succinate dehydrogenase inhibitor) under anaerobic conditions; R01343 A L-Ornithine + 2-Oxo acid <=> 2.6.1.13 L-Glutamate 5semialdehyde + L-Amino acid NO unlikely - - Arg is an essential aa in Hasal; no arg cluster found as in Napha; no homologs for both ornithine synthesis pathways; R02282 A N-Acetylornithine + LNO 2.3.1.35 Glutamate <=> unlikely L-Ornithine + N-Acetyl-L- - - Arg is an essential aa in Hasal; no arg cluster found as in Napha; no homologs for both ornithine synthesis pathways; R00261 A 4.1.1.15 L-Glutamate <=> 4-Aminobutanoate + CO2 25 glutamate R02283 A N-Acetylornithine + 2Oxoglutarate <=> 2.6.1.11 N-Acetyl-L-glutamate 5semialdehyde + LGlutamate R02649 A 2.7.2.8 R03313 A NO unlikely - - Arg is an essential aa in Hasal; no arg cluster found as in Napha; no homologs for both ornithine synthesis pathways; NO unlikely - - Arg is an essential aa in Hasal; no arg cluster found as in Napha; no homologs for both ornithine synthesis pathways; L-Glutamate 5semialdehyde + Orthophosphate + NADP+ NO 1.2.1.41 <=> unlikely L-Glutamyl 5-phosphate + NADPH + H+ - - 9827332 NMR; proline signals were detected from labeled alanine; proline signals were also detected from labeled pyruvate in the presence of malonate (succinate dehydrogenase inhibitor) under anaerobic conditions; - - Arg is an essential aa in Hasal; no arg cluster found as in Napha; no homologs for both ornithine synthesis pathways; ATP + N-Acetyl-Lglutamate <=> ADP + N-Acetyl-Lglutamate 5-phosphate L-Glutamate 5semialdehyde <=> (S)-1-Pyrroline-5carboxylate + H2O YES secure R03314 A - R03443 A N-Acetyl-L-glutamate 5semialdehyde + Orthophosphate + NADP+ NO 1.2.1.38 <=> unlikely N-Acetyl-L-glutamate 5phosphate + NADPH + H+ Aspartate family (aspartate, alanine, asparagine) react_id subsystem EC-No reaction status genes references comment R00355 A 2.6.1.1 L-Aspartate + 2-Oxoglutarate <=> Oxaloacetate + L-Glutamate YES secure OE1755F OE1944R OE2619F R00397 A 4.1.1.12 L-Aspartate <=> L-Alanine + CO2 NO unlikely - R00480 A 2.7.2.4 ATP + L-Aspartate <=> ADP + 4-Phospho-L-aspartate YES secure OE4333R - Lys is an essential aa in Hasal; OE1665R is homologous to dapA, but it would be the only gene of the diaminopimelate pathway; OE1665R might function as aldolase in the Entner-Douderoff pathway (kdgA); R00483 A 6.3.1.1 ATP + L-Aspartate + NH3 <=> AMP + Pyrophosphate + LAsparagine NO unlikely - 2752002 Asn derived from Asp in H. salinarum (labelling studies); Asn not required for protein synth; Asp loaded to tRNA amidotransf. and then amidated; R00485 A 3.5.1.1 L-Asparagine + H2O <=> 3.5.1.38 L-Aspartate + NH3 NO unlikely - 2752002 Asn derived from Asp in H. salinarum (labelling studies); Asn not required for protein synth; Asp loaded to tRNA amidotransf. and then amidated; NMR; aspartate signals were detected from labeled acetate and glycerol (but acetate/glycerol primarly used for the biosynthesis of lipids); 26 R00489 A 4.1.1.11 L-Aspartate <=> 4.1.1.15 beta-Alanine + CO2 NO questionable R00490 A 3.5.1.38 L-Aspartate <=> 4.3.1.1 Fumarate + NH3 YES likely - YES secure OE2278F 2752002 15715981 R00578 A 6.3.5.4 ATP + L-Aspartate + L-Glutamine + H2O <=> AMP + Pyrophosphate + LAsparagine + L-Glutamate R01773 A 1.1.1.3 L-Homoserine + NAD+ <=> YES L-Aspartate 4-semialdehyde + NADH secure + H+ OE4722R R01775 A 1.1.1.3 L-Homoserine + NADP+ <=> L-Aspartate 4-semialdehyde + NADPH + H+ YES secure OE4722R R02291 A 1.2.1.11 L-Aspartate 4-semialdehyde + Orthophosphate + NADP+ <=> 4-Phospho-L-aspartate + NADPH + H+ YES secure OE3063F - OE1498R is homologous to novel archaeal Tyr decarboxylase; OE1498R was formerly a Glu decarboxylase candidate; Asn derived from Asp in H. salinarum (labelling studies); Asn not required for protein synth; Asp loaded to tRNA amidotransf. and then amidated; Lys is an essential aa in Hasal; OE1665R is homologous to dapA, but it would be the only gene of the diaminopimelate pathway; OE1665R might function as aldolase in the Entner-Douderoff pathway (kdgA); Homoserine metabolism (threonine, methionine) react_id subsystem EC-No reaction S-Adenosyl-L-methionine + LHomocysteine <=> S-Adenosyl-L-homocysteine + LMethionine status genes NO unlikely references homoserine synth. via O-acetyl-hser, not O-succinyl-hser; methionine synthesis might be impaired due to folate-dependence of methionine synthase (metE); R00650 A 2.1.1.10 R00651 A O-Acetyl-L-homoserine + Methanethiol 2.5.1.49 <=> L-Methionine + Acetate YES secure OE4398F 8206953 pos_enz_activ; Met metabolized to methanthiol in Hasal; Met is an essential aa in Hasal; R00654 A 4.4.1.11 L-Methionine + H2O <=> Methanethiol + NH3 + 2-Oxobutanoate YES secure OE2173F OE2681F 8206953 OE4398F pos_enz_activ; Met metabolized to methanthiol in Hasal; Met is an essential aa in Hasal; R00751 A 4.1.2.5 L-Threonine <=> Glycine + Acetaldehyde YES secure OE4436R R00946 A 5-Methyltetrahydrofolate + L2.1.1.13 Homocysteine <=> Tetrahydrofolate + L-Methionine R00996 A 4.3.1.19 L-Threonine <=> 2-Oxobutanoate + NH3 R00999 A 2.5.1.48 O-Succinyl-L-homoserine + H2O <=> 2-Oxobutanoate + Succinate + NH3 NO unlikely - comment - homoserine synth. via O-acetyl-hser, not O-succinyl-hser; methionine synthesis might be impaired due to folate-dependence of methionine synthase (metE); YES secure OE3931R YES secure OE2173F OE2681F homoserine synth. via O-acetyl-hser, not O-succinyl-hser; methionine synthesis might be impaired due to folate-dependence of methionine synthase (metE); 27 R01001 A 4.4.1.1 L-Cystathionine + H2O <=> L-Cysteine + NH3 + 2-Oxobutanoate YES secure OE2173F OE2681F homoserine synth. via O-acetyl-hser, not O-succinyl-hser; methionine synthesis might be impaired due to folate-dependence of methionine synthase (metE); R01286 A 4.4.1.8 L-Cystathionine + H2O <=> L-Homocysteine + NH3 + Pyruvate YES secure OE2173F OE2681F homoserine synth. via O-acetyl-hser, not O-succinyl-hser; methionine synthesis might be impaired due to folate-dependence of methionine synthase (metE); R01287 A O-Acetyl-L-homoserine + Hydrogen sulfide YES 2.5.1.49 <=> secure L-Homocysteine + Acetate OE4398F - homoserine synth. via O-acetyl-hser, not O-succinyl-hser; methionine synthesis might be impaired due to folate-dependence of methionine synthase (metE); R01288 A 2.5.1.48 O-Succinyl-L-homoserine + Sulfide <=> L-Homocysteine + Succinate YES secure OE2173F OE2681F homoserine synth. via O-acetyl-hser, not O-succinyl-hser; methionine synthesis might be impaired due to folate-dependence of methionine synthase (metE); R01290 A 4.2.1.22 L-Serine + L-Homocysteine <=> L-Cystathionine + H2O YES OE1916F insecure OE2860R R01466 A 4.2.3.1 O-Phospho-L-homoserine + H2O <=> L-Threonine + Orthophosphate YES secure OE1807R OE3941F 3700337 OE4412R NMR; Thr signals were detected from labeled acetate (if Thr was omitted from the growth medium); OE4412R with best blast results; OE3941F close to OE3931R (EC 4.3.1.19) catalyzing the next pathway step of to 2oxobutanoate; R01771 A 2.7.1.39 ATP + L-Homoserine <=> ADP + O-Phospho-L-homoserine YES secure OE3531R 3700337 NMR; Thr signals were detected from labeled acetate (if Thr was omitted from the growth medium); R01776 A 2.3.1.31 Acetyl-CoA + L-Homoserine <=> CoA + O-Acetyl-L-homoserine YES secure OE4397F - homoserine synth. via O-acetyl-hser, not O-succinyl-hser; methionine synthesis might be impaired due to folate-dependence of methionine synthase (metE); R01777 A 2.3.1.46 Succinyl-CoA + L-Homoserine <=> CoA + O-Succinyl-L-homoserine NO unlikely R02821 A 2.1.1.5 Betaine + L-Homocysteine <=> N,N-Dimethylglycine + L-Methionine NO unlikely R03217 A 2.5.1.49 O-Acetyl-L-homoserine + L-Cysteine <=> L-Cystathionine + Acetate R03260 A O-Succinyl-L-homoserine + L-Cysteine 2.5.1.48 <=> L-Cystathionine + Succinate R04405 A - homoserine synth. via O-acetyl-hser, not O-succinyl-hser; methionine synthesis might be impaired due to folate-dependence of methionine synthase (metE); YES secure OE4398F - homoserine synth. via O-acetyl-hser, not O-succinyl-hser; methionine synthesis might be impaired due to folate-dependence of methionine synthase (metE); YES secure OE2173F OE2681F homoserine synth. via O-acetyl-hser, not O-succinyl-hser; methionine synthesis might be impaired due to folate-dependence of methionine synthase (metE); 5-Methyltetrahydropteroyltri-L-glutamate + L-Homocysteine <=> YES 2.1.1.14 Tetrahydropteroyltri-L-glutamate + Llikely Methionine OE2668R - homoserine synth. via O-acetyl-hser, not O-succinyl-hser; methionine synthesis might be impaired due to folate-dependence of methionine synthase (metE); Lysine biosynthesis react_id subsystem EC-No reaction status genes references comment R00271 A 2-Hydroxybutane-1,2,4-tricarboxylate + NO 2.3.3.14 CoA <=> unlikely Acetyl-CoA + H2O + 2-Oxoglutarate - Lys is an essential aa in Hasal; no enzyme for both pathways found; R00451 A 4.1.1.20 meso-2,6-Diaminoheptanedioate <=> - Lys is an essential aa in Hasal; no enzyme for both pathways found; NO - 28 L-Lysine + CO2 unlikely R00457 A L-Lysine + 2-Oxoglutarate <=> NO 2.6.1.36 L-2-Aminoadipate 6-semialdehyde + Lunlikely Glutamate - Lys is an essential aa in Hasal; no enzyme for both pathways found; R00715 A 1.5.1.7 N6-(L-1,3-Dicarboxypropyl)-L-lysine + NAD+ + H2O <=> NO L-Lysine + 2-Oxoglutarate + NADH + unlikely H+ - Lys is an essential aa in Hasal; no enzyme for both pathways found; R00716 A 1.5.1.8 N6-(L-1,3-Dicarboxypropyl)-L-lysine + NADP+ + H2O <=> NO L-Lysine + 2-Oxoglutarate + NADPH + unlikely H+ - Lys is an essential aa in Hasal; no enzyme for both pathways found; R01934 A 1.1.1.87 Homoisocitrate + NAD+ <=> 2-Oxoadipate + CO2 + NADH NO unlikely - Lys is an essential aa in Hasal; no enzyme for both pathways found; R01939 A L-2-Aminoadipate + 2-Oxoglutarate 2.6.1.39 <=> 2-Oxoadipate + L-Glutamate NO unlikely - Lys is an essential aa in Hasal; no enzyme for both pathways found; R02292 A L-Aspartate 4-semialdehyde + Pyruvate NO 4.2.1.52 <=> possible 2,3-Dihydrodipicolinate + 2 H2O - Lys is an essential aa in Hasal; OE1665R is homologous to dapA, but it would be the only gene of the diaminopimelate pathway; OE1665R might function as aldolase in the EntnerDouderoff pathway (kdgA); R02315 A N6-(L-1,3-Dicarboxypropyl)-L-lysine + NADP+ + H2O <=> NO 1.5.1.10 L-Glutamate + L-2-Aminoadipate 6unlikely semialdehyde + NADPH + H+ - Lys is an essential aa in Hasal; no enzyme for both pathways found; R02733 A N6-Acetyl-LL-2,6NO 3.5.1.47 diaminoheptanedioate + H2O <=> unlikely Acetate + LL-2,6-Diaminoheptanedioate - Lys is an essential aa in Hasal; no enzyme for both pathways found; R02734 A N-Succinyl-LL-2,6diaminoheptanedioate + H2O <=> 3.5.1.18 Succinate + LL-2,6Diaminoheptanedioate NO unlikely - Lys is an essential aa in Hasal; no enzyme for both pathways found; R02735 A 5.1.1.7 NO unlikely - Lys is an essential aa in Hasal; no enzyme for both pathways found; R02755 A meso-2,6-Diaminoheptanedioate + NADP+ + H2O <=> 1.4.1.16 L-2-Amino-6-oxoheptanedioate + NH3 + NADPH NO unlikely - Lys is an essential aa in Hasal; no enzyme for both pathways found; R03098 A 1.2.1.31 L-2-Aminoadipate + ATP <=> NO - Lys is an essential aa in Hasal; no enzyme for both pathways found; LL-2,6-Diaminoheptanedioate <=> meso-2,6-Diaminoheptanedioate - 29 L-2-Aminoadipate adenylate + Pyrophosphate unlikely R03444 A 2-Hydroxybutane-1,2,4-tricarboxylate 4.2.1.36 <=> But-1-ene-1,2,4-tricarboxylate + H2O NO unlikely - Lys is an essential aa in Hasal; no enzyme for both pathways found; R04198 A 2,3,4,5-Tetrahydrodipicolinate + NAD+ NO 1.3.1.26 <=> unlikely 2,3-Dihydrodipicolinate + NADH + H+ - Lys is an essential aa in Hasal; no enzyme for both pathways found; R04199 A 2,3,4,5-Tetrahydrodipicolinate + NADP+ <=> 1.3.1.26 2,3-Dihydrodipicolinate + NADPH + H+ NO unlikely - Lys is an essential aa in Hasal; no enzyme for both pathways found; R04336 A - L-2-Amino-6-oxoheptanedioate <=> 2,3,4,5-Tetrahydrodipicolinate + H2O NO unlikely - Lys is an essential aa in Hasal; no enzyme for both pathways found; R04364 A 2,3,4,5-Tetrahydrodipicolinate + Acetyl2.3.1.CoA <=> NO 2.3.1.89 N-Acetyl-L-2-amino-6-oxopimelate + unlikely CoA - Lys is an essential aa in Hasal; no enzyme for both pathways found; R04365 A Succinyl-CoA + 2,3,4,5Tetrahydrodipicolinate + H2O <=> 2.3.1.117 CoA + N-Succinyl-2-L-amino-6oxoheptanedioate NO unlikely - Lys is an essential aa in Hasal; no enzyme for both pathways found; R04371 A 4.2.1.36 Homoisocitrate <=> But-1-ene-1,2,4-tricarboxylate + H2O NO unlikely - Lys is an essential aa in Hasal; no enzyme for both pathways found; R04390 A alpha-Aminoadipoyl-S-acyl enzyme + NADPH + H+ <=> 1.2.1.31 L-2-Aminoadipate 6-semialdehyde + Holo-Lys2 + NADP+ NO unlikely - Lys is an essential aa in Hasal; no enzyme for both pathways found; R04467 A 2.6.1.- N6-Acetyl-LL-2,6diaminoheptanedioate + 2-Oxoglutarate NO <=> unlikely N-Acetyl-L-2-amino-6-oxopimelate + L-Glutamate - Lys is an essential aa in Hasal; no enzyme for both pathways found; R04475 A N-Succinyl-LL-2,6diaminoheptanedioate + 2-Oxoglutarate NO 2.6.1.17 <=> unlikely N-Succinyl-2-L-amino-6oxoheptanedioate + L-Glutamate - Lys is an essential aa in Hasal; no enzyme for both pathways found; 30 R04863 A L-2-Aminoadipate adenylate + HoloLys2 <=> 1.2.1.31 alpha-Aminoadipoyl-S-acyl enzyme + AMP NO unlikely - Lys is an essential aa in Hasal; no enzyme for both pathways found; Serine family (serine, glycine, cysteine) react_id subsystem EC-No reaction status genes references comment R00582 A 3.1.3.3 O-Phospho-L-serine + H2O <=> L-Serine + Orthophosphate YES secure OE4405R - NMR; Ser signals detected from labeled substrates; pathways via hydroxypyruvate/3P-hydroxypyruvate incomplete; pathway via 3P-hydroxypyruvate likely, since genes for EC 1.1.1.95 and EC 3.1.3.3 adjacent to each other; missing EC 2.6.1.52 potentially coded by OE4391F; serine dehydratation to pyruvate by EC 4.3.1.19 might be possible; R00585 A 2.6.1.51 L-Serine + Pyruvate <=> Hydroxypyruvate + L-Alanine YES OE4391F insecure NMR; Ser signals detected from labeled substrates; pathways via hydroxypyruvate/3P-hydroxypyruvate incomplete; pathway via 3P-hydroxypyruvate likely, since genes for EC 1.1.1.95 and EC 3.1.3.3 adjacent to each other; missing EC 2.6.1.52 potentially coded by OE4391F; serine dehydratation to pyruvate by EC 4.3.1.19 might be possible; R00586 A 2.3.1.30 L-Serine + Acetyl-CoA <=> O-Acetyl-L-serine + CoA YES secure OE3122F R00897 A O-Acetyl-L-serine + Hydrogen 2.5.1.47 sulfide <=> L-Cysteine + Acetate YES secure OE1916F OE2860R R00945 A 2.1.2.1 YES secure OE3036F R01388 A 1.1.1.29 D-Glycerate + NAD+ <=> 1.1.1.81 Hydroxypyruvate + NADH + H+ R01392 A 1.1.1.81 R01513 A 3-Phospho-D-glycerate + NAD+ <=> 1.1.1.95 3-Phosphonooxypyruvate + NADH + H+ R01514 C 2.7.1.31 R04173 A O-Phospho-L-serine + 2Oxoglutarate <=> 2.6.1.52 3-Phosphonooxypyruvate + LGlutamate 5,10-Methylenetetrahydrofolate + Glycine + H2O <=> Tetrahydrofolate + L-Serine NO possible - NMR; Ser signals detected from labeled substrates; pathways via hydroxypyruvate/3P-hydroxypyruvate incomplete; pathway via 3P-hydroxypyruvate likely, since genes for EC 1.1.1.95 and EC 3.1.3.3 adjacent to each other; missing EC 2.6.1.52 potentially coded by OE4391F; serine dehydratation to pyruvate by EC 4.3.1.19 might be possible; D-Glycerate + NADP+ <=> NO Hydroxypyruvate + NADPH + H+ unlikely - NMR; Ser signals detected from labeled substrates; pathways via hydroxypyruvate/3P-hydroxypyruvate incomplete; pathway via 3P-hydroxypyruvate likely, since genes for EC 1.1.1.95 and EC 3.1.3.3 adjacent to each other; missing EC 2.6.1.52 potentially coded by OE4391F; serine dehydratation to pyruvate by EC 4.3.1.19 might be possible; OE4408F - NMR; Ser signals detected from labeled substrates; pathways via hydroxypyruvate/3P-hydroxypyruvate incomplete; pathway via 3P-hydroxypyruvate likely, since genes for EC 1.1.1.95 and EC 3.1.3.3 adjacent to each other; missing EC 2.6.1.52 potentially coded by OE4391F; serine dehydratation to pyruvate by EC 4.3.1.19 might be possible; ATP + D-Glycerate <=> ADP + 3-Phospho-D-glycerate YES secure NO unlikely YES OE4391F insecure NMR; Ser signals detected from labeled substrates; pathways via hydroxypyruvate/3P-hydroxypyruvate incomplete; pathway via 3P-hydroxypyruvate likely, since genes for EC 1.1.1.95 and EC 3.1.3.3 adjacent to each other; missing EC 2.6.1.52 potentially coded by OE4391F; serine dehydratation to pyruvate by EC 4.3.1.19 might be possible; 31 Biosynthesis of branched chain amino acids (valine, leucine, isoleucine) react_id subsystem EC-No reaction status genes references comment R00014 C 1.2.4.1 2.2.1.6 2-(alpha-Hydroxyethyl)thiamine diphosphate + CO2 <=> Thiamin diphosphate + Pyruvate NO unlikely TU_oxdhA1B_dsa_lpdA; 4 subunits likely to form a 2-oxoacid dehydrogenase complex; not pyruvate or 215556640 oxoglutarate dh complex (lipoic acid absent in H. salinarum pyruvate and 2-oxoglutarate synthase); 2-oxoacid 6266826 dehydrogenase complex might be involved in branched-chain amino acid degradation as in T. acidophilum; R01088 A 1.4.1.9 L-Leucine + H2O + NAD+ <=> 4-Methyl-2-oxopentanoate + NH3 + NADH NO unlikely - R01090 A L-Leucine + 2-Oxoglutarate <=> 2.6.1.6 4-Methyl-2-oxopentanoate + L2.6.1.42 Glutamate YES secure R01213 A 2-Isopropylmalate + CoA <=> 2.3.3.13 Acetyl-CoA + 3-Methyl-2oxobutanoate + H2O NO unlikely R01214 A L-Valine + 2-Oxoglutarate <=> 2.6.1.42 3-Methyl-2-oxobutanoate + LGlutamate YES secure R01215 A L-Valine + Pyruvate <=> 2.6.1.66 3-Methyl-2-oxobutanoate + LAlanine NO unlikely - Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; R01434 A 1.4.1.9 L-Valine + H2O + NAD+ <=> 3-Methyl-2-oxobutanoate + NH3 + NADH NO unlikely - Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; R01652 A - 4-Methyl-2-oxopentanoate + CO2 <=> 3-Carboxy-4-methyl-2oxopentanoate NO unlikely - Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; R02196 A 1.4.1.9 L-Isoleucine + NAD+ + H2O <=> (R)-2-Oxo-3-methylpentanoate + NH3 + NADH NO unlikely - Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; R02199 A L-Isoleucine + 2-Oxoglutarate <=> 2.6.1.42 (R)-2-Oxo-3-methylpentanoate + LGlutamate R03968 A 4.2.1.33 2-Isopropylmalate <=> 2-Isopropylmaleate + H2O NO OE1020F unlikely Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; R04001 A 4.2.1.33 3-Isopropylmalate <=> 2-Isopropylmaleate + H2O NO OE1020F unlikely Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; R04426 A 3-Isopropylmalate + NAD+ <=> 1.1.1.85 3-Carboxy-4-methyl-2oxopentanoate + NADH + H+ NO unlikely - Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; R04440 A 1.1.1.86 (R)-2,3-Dihydroxy-3- NO - Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; YES secure OE3959R - - OE3959R - OE3959R - - Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; 2.6.1.42 required for Val, Leu, Ile degradation; no enzymes for synth. pathways found; no_seq for 2.6.1.6.; Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; 2.6.1.42 required for Val, Leu, Ile degradation; no enzymes for synth. pathways found; no_seq for 2.6.1.6.; 2.6.1.42 required for Val, Leu, Ile degradation; no enzymes for synth. pathways found; no_seq for 2.6.1.6.; 32 methylbutanoate + NADP+ <=> (R)-3-Hydroxy-3-methyl-2oxobutanoate + NADPH unlikely R04441 A 4.2.1.9 (R)-2,3-Dihydroxy-3methylbutanoate <=> 3-Methyl-2-oxobutanoate + H2O NO unlikely - Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; R04672 A 2.2.1.6 (S)-2-Acetolactate + Thiamin diphosphate <=> 2-(alpha-Hydroxyethyl)thiamine diphosphate + Pyruvate NO unlikely - Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; R04673 A 2.2.1.6 2-Oxobutanoate + 2-(alphaHydroxyethyl)thiamine diphosphate <=> (S)-2-Aceto-2-hydroxybutanoate + Thiamin diphosphate NO unlikely - Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; R05068 A 1.1.1.86 (R)-2,3-Dihydroxy-3methylpentanoate + NADP+ <=> (S)-2-Hydroxy-3-methyl-3oxopentanoate + NADPH NO unlikely - Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; R05069 A (S)-2-Aceto-2-hydroxybutanoate <=> 1.1.1.86 (S)-2-Hydroxy-3-methyl-3oxopentanoate NO unlikely - Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; R05070 A 4.2.1.9 (R)-2,3-Dihydroxy-3methylpentanoate <=> (R)-2-Oxo-3-methylpentanoate + H2O NO unlikely - Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; R05071 A (S)-2-Acetolactate <=> 1.1.1.86 (R)-3-Hydroxy-3-methyl-2oxobutanoate NO unlikely - Val, Leu, Ile are essential amino acids in Hasal; no enzymes for synth. pathways found; Shikimate pathway and biosynthesis of aromatic amino acids (phenylalanine, tyrosine, tryptophan) react_id subsystem EC-No reaction status genes references R00996 A 4.3.1.19 L-Threonine <=> 2-Oxobutanoate + NH3 YES secure OE3931R R01714 A 4.2.3.5 5-O-(1-Carboxyvinyl)-3phosphoshikimate <=> Chorismate + Orthophosphate YES secure OE2761R 3700337 R01826 A Phosphoenolpyruvate + D2.5.1.54 Erythrose 4-phosphate + H2O <=> NO unlikely comment NMR; phenylalanine signals were detected from labeled glycerol; Phe synthesis likely via shikimate pathway; first enzyme of the shikimate pathway; missing in all archaea; all enzymes from 3-dehydroquinate to shikimate present; 9324245 presumably alternative pathway in some archaea for sythesis of 3-dehydroquinate; labeling studies in M. marispaludis 11114929 showed that erythrose 4-P is not a precurser of chorismate; 33 2-Dehydro-3-deoxy-D-arabinoheptonate 7-phosphate + Orthophosphate R02412 A 2.7.1.71 ATP + Shikimate <=> ADP + Shikimate 3-phosphate YES secure OE2785R 3700337 NMR; phenylalanine signals were detected from labeled glycerol; Phe synthesis likely via shikimate pathway; R02413 A Shikimate + NADP+ <=> YES 1.1.1.25 3-Dehydroshikimate + NADPH + secure H+ OE1565F 3700337 NMR; phenylalanine signals were detected from labeled glycerol; Phe synthesis likely via shikimate pathway; R03083 A 4.2.3.4 2-Dehydro-3-deoxy-D-arabinoheptonate 7-phosphate <=> 3-Dehydroquinate + Orthophosphate NO unlikely R03084 A 4.2.1.10 3-Dehydroquinate <=> 3-Dehydroshikimate + H2O YES secure OE1477R 3700337 NMR; phenylalanine signals were detected from labeled glycerol; Phe synthesis likely via shikimate pathway; R03460 A Phosphoenolpyruvate + Shikimate 3-phosphate <=> 2.5.1.19 Orthophosphate + 5-O-(1Carboxyvinyl)-3phosphoshikimate YES secure OE2762R 3700337 NMR; phenylalanine signals were detected from labeled glycerol; Phe synthesis likely via shikimate pathway; R10011 A - L-Aspartate 4-semialdehyde <=> YES 3-Dehydroquinate secure L-Asp semialdehyde and DKFP are precursers of the archaeal shikimate pathway; step 1: L-aspartate semialdehyde + 615182204 deoxy-5-ketofructose-1-phosphate => 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonic acid (OE1472F); step 2: 2-amino2752002 3,7-dideoxy-D-threo-hept-6-ulosonic acid => 3-dehydroquinate (OE1475F); the two required enzyme genes are adjacent 1968385 to each other; labeled Asp incorporated into Trp in H. salinarum; pabABC clustered; aminodeoxychorismate synthase (EC 6.3.5.8, pabAB) fomerly assigned as anthranilate synthase; OE1472F 15182204 pabA (OE1570F) presumably nonfunctional in strain R1 due to an interruption by an ISH element; p-aminbenzoate might OE1475F be synthesized from 3-dehydroquinate and not from chorismate in archaea (PMID:15182204); Histidine biosynthesis react_id subsystem EC-No reaction status genes references comment R01071 A Phosphoribosyl-ATP + Pyrophosphate <=> 2.4.2.17 ATP + 5-Phospho-alpha-D-ribose 1-diphosphate YES secure OE4152R 3700337 NMR; histidine signals were detected from labeled glycerol; R01163 A 1.1.1.23 L-Histidinal + H2O + 2 NAD+ <=> L-Histidine + 2 NADH + H+ YES secure OE3071F 3700337 NMR; histidine signals were detected from labeled glycerol; R03012 A 1.1.1.23 L-Histidinol + NAD+ <=> L-Histidinal + NADH + H+ YES secure OE3071F 3700337 NMR; histidine signals were detected from labeled glycerol; R03013 A 3.1.3.15 L-Histidinol phosphate + H2O <=> L-Histidinol + Orthophosphate YES insecure R03243 A 2.6.1.9 L-Histidinol phosphate + 2-Oxoglutarate <=> YES 3-(Imidazol-4-yl)-2-oxopropyl phosphate + L-Glutamate secure OE2507R 3700337 NMR; histidine signals were detected from labeled glycerol; R03457 A 4.2.1.19 D-erythro-1-(Imidazol-4-yl)glycerol 3-phosphate <=> 3-(Imidazol-4-yl)-2-oxopropyl phosphate + H2O YES secure OE4220F 3700337 NMR; histidine signals were detected from labeled glycerol; R04035 A 3.6.1.31 Phosphoribosyl-ATP + H2O <=> Phosphoribosyl-AMP + Pyrophosphate YES secure OE4641R 3700337 NMR; histidine signals were detected from labeled glycerol; - no archaeal seq; non-orthologous gene displacement in archaea might be possible; feeble hits with OE2276 and OE4492F (both without assigned function yet); bifunctional protein in other species with EC 4.2.1.19 (OE4220F); NMR; histidine signals were detected from labeled glycerol; 34 R04037 A Phosphoribosyl-AMP + H2O <=> 3.5.4.19 5-(5-Phospho-D-ribosylaminoformimino)-1-(5phosphoribosyl)- YES secure 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide + L-Glutamate + D-erythro-1-(Imidazol-4-yl)glycerol 3YES phosphate <=> secure N-(5'-Phospho-D-1'-ribulosylformimino)-5-amino-1-(5''phospho-D- + L-Glutamine R04558 A 2.4.2.- R04640 A 5-(5-Phospho-D-ribosylaminoformimino)-1-(5phosphoribosyl)- <=> YES 5.3.1.16 N-(5'-Phospho-D-1'-ribulosylformimino)-5-amino-1-(5''- secure phospho-D- OE4199R 3700337 NMR; histidine signals were detected from labeled glycerol; OE2268R OE3913F 2 steps reaction; no info about genes in KEGG; NMR; histidine signals were detected from labeled glycerol; OE4218F 3700337 NMR; histidine signals were detected from labeled glycerol; 8 Amino acid degradation react_id subsystem EC-No reaction status genes references comment R00262 A L-threo-3-Methylaspartate 5.4.99.1 <=> L-Glutamate YES secure OE4204F OE4206F R00673 A 4.1.99.1 L-Tryptophan + H2O <=> Indole + Pyruvate + NH3 YES secure OE4331R R00736 A 4.1.1.25 L-Tyrosine <=> 4.1.1.28 Tyramine + CO2 YES likely OE1498R 15715981 OE1498R is homologous to novel archaeal Tyr decarboxylase; OE1498R was formerly a Glu decarboxylase candidate; R00987 A 3.7.1.3 YES likely OE2332F R01090 A L-Leucine + 2-Oxoglutarate 2.6.1.6 <=> 2.6.1.42 4-Methyl-2-oxopentanoate + L-Glutamate YES secure OE3959R - R01168 A 4.3.1.3 L-Histidine <=> Urocanate + NH3 YES secure OE2739F R01214 A 2.6.1.42 L-Valine + 2-Oxoglutarate <=> 3-Methyl-2-oxobutanoate + L-Glutamate YES secure OE3959R - 1.2.4.4 3-Methyl-2-oxobutanoate + Lipoamide <=> S-(2-Methylpropanoyl)dihydrolipoamide + CO2 OE3712R OE4113F TU_oxdhA1B_dsa_lpdA; 4 subunits likely to form a 2-oxoacid dehydrogenase complex; not pyruvate or 2-oxoglutarate dh YES 15556640 OE4114F complex (lipoic acid absent in H. salinarum pyruvate and 2-oxoglutarate synthase); 2-oxoacid dehydrogenase complex might insecure 6266826 OE4115F be involved in branched-chain amino acid degradation as in T. acidophilum; OE4116F R01701 A L-Kynurenine + H2O <=> Anthranilate + L-Alanine mam gene cluster encoded in H. salinarum; 2.6.1.42 required for Val, Leu, Ile degradation; no enzymes for synth. pathways found; no_seq for 2.6.1.6.; 2.6.1.42 required for Val, Leu, Ile degradation; no enzymes for synth. pathways found; no_seq for 2.6.1.6.; 35 4-Methyl-2-oxopentanoate + Lipoamide <=> S-(3-Methylbutanoyl)dihydrolipoamide + CO2 OE3712R OE4113F TU_oxdhA1B_dsa_lpdA; 4 subunits likely to form a 2-oxoacid dehydrogenase complex; not pyruvate or 2-oxoglutarate dh YES 15556640 OE4114F complex (lipoic acid absent in H. salinarum pyruvate and 2-oxoglutarate synthase); 2-oxoacid dehydrogenase complex might insecure 6266826 OE4115F be involved in branched-chain amino acid degradation as in T. acidophilum; OE4116F R01702 A 1.2.4.4 R02199 A L-Isoleucine + 2-Oxoglutarate <=> YES 2.6.1.42 (R)-2-Oxo-3secure methylpentanoate + LGlutamate R02285 A 3.5.3.8 N-Formimino-L-glutamate + H2O <=> L-Glutamate + Formamide YES secure OE2736F R02288 A 3.5.2.7 4-Imidazolone-5-propanoate + H2O <=> N-Formimino-L-glutamate YES secure OE2738F - - 2-Methylpropanoyl-CoA + Dihydrolipoamide <=> S-(2-Methylpropanoyl)dihydrolipoamide + CoA YES secure OE4115F R02668 A 3.7.1.3 3-Hydroxy-L-kynurenine + H2O <=> 3-Hydroxyanthranilate + LAlanine YES likely OE2332F R02914 A 4-Imidazolone-5-propanoate 4.2.1.49 <=> Urocanate + H2O YES secure OE2734F R03174 A - 2-Methylbutanoyl-CoA + Dihydrolipoamide <=> S-(2-Methylbutanoyl)dihydrolipoamide + CoA YES secure OE4115F R03696 A 4.3.1.2 L-threo-3-Methylaspartate <=> Mesaconate + NH3 YES secure OE4207F - 3.7.1.3 Formylkynurenine + H2O <=> Formylanthranilate + LAlanine YES likely OE2332F R04097 A - 3-Methylbutanoyl-CoA + Dihydrolipoamide <=> S-(3-Methylbutanoyl)dihydrolipoamide + CoA YES secure OE4115F R04225 A 1.2.4.4 3-Methyl-2-oxopentanoate + YES OE3712R 15556640 TU_oxdhA1B_dsa_lpdA; 4 subunits likely to form a 2-oxoacid dehydrogenase complex; not pyruvate or 2-oxoglutarate dh R02662 A R03936 A OE3959R - 2.6.1.42 required for Val, Leu, Ile degradation; no enzymes for synth. pathways found; no_seq for 2.6.1.6.; - 15556640 haloarchaea encode a dihydrolipoamide S-acyltransferase (EC 2.3.1.-), which is part of 2-oxoacid dehydrogenase complex 6266826 (TU_oxdhA1B_dsa_lpdA); not part of pyruvate (EC 2.3.1.12) or 2-oxoglutarate (EC 2.3.1.61) dehydrogenase complex; 15556640 haloarchaea encode a dihydrolipoamide S-acyltransferase (EC 2.3.1.-), which is part of 2-oxoacid dehydrogenase complex 6266826 (TU_oxdhA1B_dsa_lpdA); not part of pyruvate (EC 2.3.1.12) or 2-oxoglutarate (EC 2.3.1.61) dehydrogenase complex; mam gene cluster encoded in H. salinarum; 15556640 haloarchaea encode a dihydrolipoamide S-acyltransferase (EC 2.3.1.-), which is part of 2-oxoacid dehydrogenase complex 6266826 (TU_oxdhA1B_dsa_lpdA); not part of pyruvate (EC 2.3.1.12) or 2-oxoglutarate (EC 2.3.1.61) dehydrogenase complex; 36 Lipoamide <=> S-(2-Methylbutanoyl)dihydrolipoamide + CO2 insecure OE4113F 6266826 OE4114F OE4115F OE4116F complex (lipoic acid absent in H. salinarum pyruvate and 2-oxoglutarate synthase); 2-oxoacid dehydrogenase complex might be involved in branched-chain amino acid degradation as in T. acidophilum; Arginine metabolism and urea cycle react_id subsystem EC-No reaction status genes references comment R00149 P 2 ATP + NH3 + CO2 + H2O <=> 6.3.4.16 2 ADP + Orthophosphate + Carbamoyl phosphate YES secure OE3554F OE3556R R00150 A 2.7.2.2 ATP + NH3 + CO2 <=> ADP + Carbamoyl phosphate YES secure OE5206R R00178 A 4.1.1.50 S-Adenosyl-L-methionine <=> S-Adenosylmethioninamine + CO2 NO unlikely R00551 A 3.5.3.1 L-Arginine + H2O <=> L-Ornithine + Urea NO unlikely no homolog to H. marismortui arginase genes rrnAC0383 and rrnAC0453; urea cycle therefore incomplete; 16169924 urea cycle reactions from ornithine to Arg possible; arginine used for ATP generation by the arginine deiminase pathway; R00552 A 3.5.3.6 L-Arginine + H2O <=> L-Citrulline + NH3 YES secure OE5208R 7868583 8759859 R00566 A 4.1.1.19 L-Arginine <=> Agmatine + CO2 YES likely OE3803R R00575 P 6.3.5.5 2 ATP + L-Glutamine + HCO3- + H2O <=> YES 2 ADP + Orthophosphate + L-Glutamate + secure Carbamoyl phosphate OE3554F OE3556R R00670 A 4.1.1.17 L-Ornithine <=> Putrescine + CO2 NO unlikely R00671 - 4.3.1.12 L-Ornithine <=> L-Proline + NH3 YES OE4121R insecure OE2945F R01086 A 4.3.2.1 N-(L-Arginino)succinate <=> Fumarate + L-Arginine YES secure R01157 A 3.5.3.11 Agmatine + H2O <=> Putrescine + Urea YES OE3486R insecure R01398 A 2.1.3.3 Carbamoyl phosphate + L-Ornithine <=> Orthophosphate + L-Citrulline YES secure R01920 A S-Adenosylmethioninamine + Putrescine 2.5.1.16 <=> 5'-Methylthioadenosine + Spermidine 7868583 8759859 pos_enz_activ; arginine used for ATP generation by the arginine deiminase pathway; arginine used for ATP generation by the arginine deiminase pathway; no homolog to H. marismortui arginase genes rrnAC0383 and rrnAC0453; urea cycle therefore incomplete; OE4419R 16169924 urea cycle reactions from ornithine to Arg possible; arginine used for ATP generation by the arginine deiminase pathway; OE5205R 7868583 8759859 pos_enz_activ; catabolic enzyme purif. and kinetics studied; arginine used for ATP generation by the arginine deiminase pathway; urea cycle incomplete (no arginase); pathway from ornithine to Arg possible; NO unlikely 37 ATP + L-Citrulline + L-Aspartate <=> AMP + Pyrophosphate + N-(LArginino)succinate R01954 A 6.3.4.5 R02869 A S-Adenosylmethioninamine + Spermidine 2.5.1.16 <=> 5'-Methylthioadenosine + Spermine YES secure no homolog to H. marismortui arginase genes rrnAC0383 and rrnAC0453; urea cycle therefore incomplete; OE4420R 16169924 urea cycle reactions from ornithine to Arg possible; arginine used for ATP generation by the arginine deiminase pathway; NO unlikely 9 Cofactor metabolism Porphyrine and heme synthesis react_id subsystem EC-No reaction status genes R00036 V 4.2.1.24 2 5-Aminolevulinate <=> Porphobilinogen + 2 H2O YES secure OE4262F R00084 V 2.5.1.61 4 Porphobilinogen + H2O <=> Hydroxymethylbilane + 4 NH3 YES secure OE4276F R00310 V 4.99.1.1 Protoporphyrin + Iron <=> Heme + 2 H+ NO questionable R00831 V 2.3.1.37 Succinyl-CoA + Glycine <=> 2-Amino-3-oxoadipate + CoA NO unlikely - R02270 V 2.3.1.37 2-Amino-3-oxoadipate <=> 5-Aminolevulinate + CO2 NO unlikely - R02272 V 5.4.3.8 5-Aminolevulinate <=> (S)-4-Amino-5-oxopentanoate YES secure OE4268F R02864 V 4.99.1.4 Siroheme + 2 H+ <=> Iron + Sirohydrochlorin YES insecure OE3498R R03165 V 4.2.1.75 Hydroxymethylbilane <=> Uroporphyrinogen III + H2O YES secure OE4281F R03194 V 2.1.1.107 2 S-Adenosyl-L-methionine + Uroporphyrinogen III <=> 2 S-Adenosyl-L-homocysteine + Precorrin 2 YES secure OE4277F R03197 V 4.1.1.37 Uroporphyrinogen III <=> Coproporphyrinogen III + 4 CO2 R03220 V 1.3.3.3 R03222 V R03947 V references comment - hemEFGH and hemN missing in Hasal; hemY questionable; NO questionable - hemEFGH and hemN missing in Hasal; hemY questionable; Coproporphyrinogen III + Oxygen <=> Protoporphyrinogen IX + 2 CO2 + 2 H2O NO questionable - hemEFGH and hemN missing in Hasal; hemY questionable; 1.3.3.4 2 Protoporphyrinogen IX + 3 Oxygen <=> 2 Protoporphyrin + 6 H2O YES insecure OE3533F - hemEFGH and hemN missing in Hasal; hemY questionable; 1.3.1.76 Precorrin 2 + NAD+ <=> Sirohydrochlorin + NADH + H+ YES secure OE3498R 38 R04109 V 1.2.1.- L-Glutamyl-tRNA(Glu) + NADPH <=> YES (S)-4-Amino-5-oxopentanoate + tRNA(Glu) + NADP+ + H2O secure OE3496R R05578 V 6.1.1.17 tRNA(Glu) + L-Glutamate + ATP <=> L-Glutamyl-tRNA(Glu) + Pyrophosphate + AMP YES secure OE2652F R07411 V 2.5.1.- Heme <=> Heme O YES insecure - R07412 V - Heme O <=> Heme A YES likely OE3306R 16989823 distant homolog of archaeal-type heme A synthase; Cobamide synthesis react_id subsystem EC-No reaction status genes references R01734 V - Dimethylbenzimidazole <=> Riboflavin YES likely OE2364R 16537439 R03947 V 1.3.1.76 Precorrin 2 + NAD+ <=> Sirohydrochlorin + NADH + H+ YES secure OE3498R 2.1.1.130 S-Adenosyl-L-methionine + Precorrin 2 <=> S-Adenosyl-L-homocysteine + Precorrin 3A YES secure OE3209F R04148 V 2.4.2.21 Nicotinate D-ribonucleotide + Dimethylbenzimidazole <=> Nicotinate + N1-(5-Phospho-alpha-Dribosyl)-5,6-dimethylbenzimidazole YES likely OE3242F - R04594 V 3.1.3.73 N1-(5-Phospho-alpha-D-ribosyl)-5,6dimethylbenzimidazole + H2O <=> alpha-Ribazole + Orthophosphate YES insecure R05149 V 2.1.1.132 2 S-Adenosyl-L-methionine + Precorrin 6Y <=> 2 S-Adenosyl-L-homocysteine + Precorrin 8X + CO2 YES secure R05150 V 1.3.1.54 Precorrin 6Y + NADP+ <=> Precorrin 6X + NADPH YES insecure R05177 V 5.4.1.2 Precorrin 8X <=> Hydrogenobyrinate YES secure OE3237F R05180 V 2.1.1.131 S-Adenosyl-L-methionine + Precorrin 3B <=> S-Adenosyl-L-homocysteine + Precorrin 4 YES secure OE3214F OE3216F R05181 V 2.1.1.133 S-Adenosyl-L-methionine + Precorrin 4 <=> YES secure OE3212F R03948 V 16547066 OE3207F OE3238F - comment reaction should be updated: FMN <=> dimethylbenzimidazole + erythrose-4P; reaction catalyzed by BluB; distant homolog found in H. salinarum; cobT in SALTY, cobU in PSEDE; no genetic evidence; cobC in SALTY; cobC homolog only present in other haloarchaea, e.g. NP1332A; novel archaeal-type enzyme cobZ absent in all haloarchaea; EC 2.1.1.132 catalyzes 2 steps: precorrin-6Y to -8W to -8X; first step cbiE/cobL1 (Nterm) (OE3238F), second step cbiT/cobL2 (Cterm) (OE3207F); cbiJ in SALTY, cobK in PSEDE; 39 S-Adenosyl-L-homocysteine + Precorrin 5 R05217 V 1.14.13.83 Precorrin 3A + Oxygen <=> Precorrin 3B YES insecure R05218 V 1.16.8.1 Cob(II)yrinate a,c diamide + H+ + NADH <=> Cob(I)yrinate a,c diamide + NAD+ YES insecure R05219 V 2.1.1.152 Precorrin 6X + Acetate + S-AdenosylL-homocysteine <=> Precorrin 5 + S-Adenosyl-Lmethionine + H2O YES insecure R05220 V 2.5.1.17 Cob(I)yrinate a,c diamide + ATP <=> Adenosyl cobyrinate a,c diamide + Pyrophosphate + Orthophosphate YES secure R05221 V 2.7.1.156 Adenosyl cobinamide + ATP <=> Adenosyl cobinamide phosphate + ADP NO unlikely R05222 V 2.7.7.62 Adenosyl cobinamide phosphate + GTP <=> Adenosine-GDP-cobinamide + Pyrophosphate YES secure archaeal cob synthesis different from bacteria: R05225 (cbiP), R06529 (cbiB), R05222 (cobY), R05223 (cobS); 12486068 bacterial-type bifunctional cob enzyme (cobU in SALTY, cobP in PSEDE) missing in archaea; novel archaealOE3257F 14645280 type enzymes cbiZ (OE3261F) and cobY (OE3257F) replace cobU; mutant study of cbiP (OE3246F) and cbiB 14990804 (OE3253F) done for H. salinarum; R05223 V 2.7.8.26 Cobamide coenzyme + GMP <=> Adenosine-GDP-cobinamide + alphaRibazole YES secure OE3255F - 6.3.5.9 Hydrogenobyrinate + 2 L-Glutamine + 2 ATP + 2 H2O <=> YES Hydrogenobyrinate a,c diamide + 2 secure Orthophosphate + 2 L-Glutamate + 2 ADP OE3243F R05225 V 6.3.5.10 Adenosyl cobyrinate a,c diamide + 4 L-Glutamine + 4 ATP <=> YES Adenosyl cobyrinate hexaamide + 4 Lsecure Glutamate + 4 Orthophosphate + 4 ADP archaeal cob synthesis different from bacteria: R05225 (cbiP), R06529 (cbiB), R05222 (cobY), R05223 (cobS); 12486068 bacterial-type bifunctional cob enzyme (cobU in SALTY, cobP in PSEDE) missing in archaea; novel archaealOE3246F 14645280 type enzymes cbiZ (OE3261F) and cobY (OE3257F) replace cobU; mutant study of cbiP (OE3246F) and cbiB 14990804 (OE3253F) done for H. salinarum; R05226 V 6.3.1.10 Adenosyl cobyrinate hexaamide + 1Aminopropan-2-ol <=> Adenosyl cobinamide NO possible R05227 V 6.6.1.2 Hydrogenobyrinate a,c diamide + Cobalt + ATP <=> Cob(II)yrinate a,c diamide + Orthophosphate + ADP YES secure R05224 V - cobG in PSEDE; - cobF in PSEDE; OE3245F - btuR in SALTU, cobO in PSEDE; archaeal cob synthesis different from bacteria: R05225 (cbiP), R06529 (cbiB), R05222 (cobY), R05223 (cobS); 12486068 bacterial-type bifunctional cob enzyme (cobU in SALTY, cobP in PSEDE) missing in archaea; novel archaeal14645280 type enzymes cbiZ (OE3261F) and cobY (OE3257F) replace cobU; mutant study of cbiP (OE3246F) and cbiB 14990804 (OE3253F) done for H. salinarum; cobS in SALTY, cobV in PSEDE; archaeal cob synthesis different from bacteria: R05225 (cbiP), R06529 (cbiB), R05222 (cobY), R05223 (cobS); 12486068 bacterial-type bifunctional cob enzyme (cobU in SALTY, cobP in PSEDE) missing in archaea; novel archaeal14645280 type enzymes cbiZ (OE3261F) and cobY (OE3257F) replace cobU; mutant study of cbiP (OE3246F) and cbiB 14990804 (OE3253F) done for H. salinarum; OE3230F 40 R05807 V 4.99.1.3 Sirohydrochlorin + Cobalt <=> Cobalt-precorrin 2 YES secure OE3221F - R05808 V 2.1.1.130 Cobalt-precorrin 2 + S-Adenosyl-Lmethionine <=> Cobalt-precorrin 3 + S-Adenosyl-Lhomocysteine YES secure OE3209F R05809 V 2.1.1.131 Cobalt-precorrin 3 + S-Adenosyl-Lmethionine <=> Cobalt-precorrin 4 + S-Adenosyl-Lhomocysteine YES secure OE3214F OE3216F R05810 V 2.1.1.133 Cobalt-precorrin 4 + S-Adenosyl-Lmethionine <=> Cobalt-precorrin 5 + S-Adenosyl-Lhomocysteine YES secure OE3212F R05811 V 2.1.1.2.1.1.152 Cobalt-precorrin 5 + S-Adenosyl-Lmethionine + H2O <=> Cobalt-precorrin 6 + S-Adenosyl-Lhomocysteine + Acetaldehyde YES insecure R05812 V 1.3.1.54 Cobalt-precorrin 6 + NADPH + H+ <=> Cobalt-dihydro-precorrin 6 + NADP+ YES insecure R05813 V 2.1.1.132 Cobalt-dihydro-precorrin 6 + 2 SAdenosyl-L-methionine <=> Cobalt-precorrin 8 + 2 S-Adenosyl-Lhomocysteine + CO2 YES secure OE3207F OE3238F R05814 V 5.4.1.2 Cobalt-precorrin 8 <=> Cobyrinate YES secure OE3237F R05815 V 6.3.1.6.3.5.9 Cobyrinate + 2 L-Glutamine + 2 ATP + 2 H2O <=> Cob(II)yrinate a,c diamide + 2 LGlutamate + 2 ADP + 2 Orthophosphate YES secure OE3243F R06529 V 6.3.1.10 Adenosyl cobyrinate hexaamide + D-1Aminopropan-2-ol O-phosphate + ATP YES <=> secure Adenosyl cobinamide phosphate + ADP + Orthophosphate R06530 V 4.1.1.81 L-Threonine O-3-phosphate <=> YES D-1-Aminopropan-2-ol O-phosphate + OE3259F insecure CO2 R06531 V - L-Threonine <=> L-Threonine O-3-phosphate - cbiK in SALTY, non-orthologous cbiK in BACME; cbiX homolog (OE3221F) in Hasal, not cbiK; cbiJ in SALTY, cobK in PSEDE; EC 2.1.1.132 catalyzes 2 steps: precorrin-6Y to -8W to -8X; first step cbiE/cobL1 (Nterm) (OE3238F), second step cbiT/cobL2 (Cterm) (OE3207F); archaeal cob synthesis different from bacteria: R05225 (cbiP), R06529 (cbiB), R05222 (cobY), R05223 (cobS); 12486068 bacterial-type bifunctional cob enzyme (cobU in SALTY, cobP in PSEDE) missing in archaea; novel archaealOE3253F 14645280 type enzymes cbiZ (OE3261F) and cobY (OE3257F) replace cobU; mutant study of cbiP (OE3246F) and cbiB 14990804 (OE3253F) done for H. salinarum; cobD in SALTY, cobC in PSEDE; YES insecure 41 R06558 V 2.7.1.156 Adenosyl cobinamide + GTP <=> Adenosyl cobinamide phosphate + GDP NO unlikely archaeal cob synthesis different from bacteria: R05225 (cbiP), R06529 (cbiB), R05222 (cobY), R05223 (cobS); 12486068 bacterial-type bifunctional cob enzyme (cobU in SALTY, cobP in PSEDE) missing in archaea; novel archaeal14645280 type enzymes cbiZ (OE3261F) and cobY (OE3257F) replace cobU; mutant study of cbiP (OE3246F) and cbiB 14990804 (OE3253F) done for H. salinarum; Folate synthesis and metabolism react_id subsystem EC-No R00428 V R00936 V R00937 V reaction GTP + H2O <=> 3.5.4.16 Formamidopyrimidine nucleoside triphosphate status genes references comment YES OE3673F insecure no GTP cyclohydrolase I (folE) in haloarchaea except on H. marismortui plasmid (pNG7382); new class of 17032654 GTP cyclohydrolase (MptA-type) is probably involved in folate/pterine synthesis in archaea; MptA results 17497938 in different cyclic phosphate product; alternative enzyme genes for folB and folK likely; OE1615R canonical dihydrofolate reductase (FolA) in many haloarchaea, e.g. NP2922A, alternative pathway for THF synthesis in H. salinarum; 1) dipteroate synthesis by FolP (single domain protein OE2921R and 15554970 multidomain protein OE1615R); 2) dipteroate reduced to tetrapteraote by FMN-binding Prd linker domain 17416665 of FolC-Prd-FolP fusion protein (OE1615R) ; 3) tetrapteroate converted to THF by FolC-domain (OE1615R); OE1615R canonical dihydrofolate reductase (FolA) in many haloarchaea, e.g. NP2922A, alternative pathway for THF synthesis in H. salinarum; 1) dipteroate synthesis by FolP (single domain protein OE2921R and 15554970 multidomain protein OE1615R); 2) dipteroate reduced to tetrapteraote by FMN-binding Prd linker domain 17416665 of FolC-Prd-FolP fusion protein (OE1615R) ; 3) tetrapteroate converted to THF by FolC-domain (OE1615R); OE1615R canonical dihydrofolate reductase (FolA) in many haloarchaea, e.g. NP2922A, alternative pathway for THF synthesis in H. salinarum; 1) dipteroate synthesis by FolP (single domain protein OE2921R and 15554970 multidomain protein OE1615R); 2) dipteroate reduced to tetrapteraote by FMN-binding Prd linker domain 17416665 of FolC-Prd-FolP fusion protein (OE1615R) ; 3) tetrapteroate converted to THF by FolC-domain (OE1615R); OE1615R canonical dihydrofolate reductase (FolA) in many haloarchaea, e.g. NP2922A, alternative pathway for THF synthesis in H. salinarum; 1) dipteroate synthesis by FolP (single domain protein OE2921R and 15554970 multidomain protein OE1615R); 2) dipteroate reduced to tetrapteraote by FMN-binding Prd linker domain 17416665 of FolC-Prd-FolP fusion protein (OE1615R) ; 3) tetrapteroate converted to THF by FolC-domain (OE1615R); 1.5.1.3 Tetrahydrofolate + NAD+ <=> Dihydrofolate + NADH + H+ YES secure 1.5.1.3 Tetrahydrofolate + NAD+ <=> Folic acid + NADH YES secure 1.5.1.3 Tetrahydrofolate + NADP+ <=> Dihydrofolate + NADPH + H+ YES secure R00940 V 1.5.1.3 Tetrahydrofolate + NADP+ <=> Folic acid + NADPH YES secure R01716 V 6.3.5.8 Chorismate + L-Glutamine <=> YES 4-amino-4-deoxychorismate + L-Glutamate likely R02235 V 1.5.1.3 Dihydrofolate + NAD+ <=> Folic acid + NADH + H+ YES secure OE1615R canonical dihydrofolate reductase (FolA) in many haloarchaea, e.g. NP2922A, alternative pathway for THF synthesis in H. salinarum; 1) dipteroate synthesis by FolP (single domain protein OE2921R and 15554970 multidomain protein OE1615R); 2) dipteroate reduced to tetrapteraote by FMN-binding Prd linker domain 17416665 of FolC-Prd-FolP fusion protein (OE1615R) ; 3) tetrapteroate converted to THF by FolC-domain (OE1615R); R02236 V 1.5.1.3 Dihydrofolate + NADP+ <=> Folic acid + NADPH + H+ YES secure OE1615R canonical dihydrofolate reductase (FolA) in many haloarchaea, e.g. NP2922A, alternative pathway for THF 15554970 synthesis in H. salinarum; 1) dipteroate synthesis by FolP (single domain protein OE2921R and 17416665 multidomain protein OE1615R); 2) dipteroate reduced to tetrapteraote by FMN-binding Prd linker domain R00939 V pabABC clustered; aminodeoxychorismate synthase (EC 6.3.5.8, pabAB) fomerly assigned as anthranilate OE1568F synthase; pabA (OE1570F) presumably nonfunctional in strain R1 due to an interruption by an ISH OE1570F 15182204 element; p-aminbenzoate might be synthesized from 3-dehydroquinate and not from chorismate in archaea OE1573A1F (PMID:15182204); 42 of FolC-Prd-FolP fusion protein (OE1615R) ; 3) tetrapteroate converted to THF by FolC-domain (OE1615R); R02237 V 6.3.2.17 ATP + Dihydropteroate + L-Glutamate <=> YES 6.3.2.12 ADP + Orthophosphate + Dihydrofolate secure R03067 V 2-Amino-7,8-dihydro-4-hydroxy-6(diphosphooxymethyl)pteridine + 42.5.1.15 Aminobenzoate <=> Pyrophosphate + Dihydropteroate R03503 V 2.7.6.3 R03504 V 2-Amino-4-hydroxy-6-(D-erythro-1,2,3trihydroxypropyl)-7,8- <=> 4.1.2.25 Glycolaldehyde + 2-Amino-4-hydroxy-6hydroxymethyl-7,8-dihydropteridine YES secure OE1615R canonical dihydrofolate reductase (FolA) in many haloarchaea, e.g. NP2922A, alternative pathway for THF synthesis in H. salinarum; 1) dipteroate synthesis by FolP (single domain protein OE2921R and 15554970 multidomain protein OE1615R); 2) dipteroate reduced to tetrapteraote by FMN-binding Prd linker domain 17416665 of FolC-Prd-FolP fusion protein (OE1615R) ; 3) tetrapteroate converted to THF by FolC-domain (OE1615R); OE1615R OE2921R canonical dihydrofolate reductase (FolA) in many haloarchaea, e.g. NP2922A, alternative pathway for THF synthesis in H. salinarum; 1) dipteroate synthesis by FolP (single domain protein OE2921R and 15554970 multidomain protein OE1615R); 2) dipteroate reduced to tetrapteraote by FMN-binding Prd linker domain 17416665 of FolC-Prd-FolP fusion protein (OE1615R) ; 3) tetrapteroate converted to THF by FolC-domain (OE1615R); ATP + 2-Amino-4-hydroxy-6hydroxymethyl-7,8-dihydropteridine <=> YES AMP + 2-Amino-7,8-dihydro-4-hydroxy-6- insecure (diphosphooxymethyl)pteridine YES insecure R04620 V 3.1.3.1 2-Amino-4-hydroxy-6-(erythro-1,2,3trihydroxypropyl) + 3 H2O <=> 2-Amino-4-hydroxy-6-(D-erythro-1,2,3trihydroxypropyl)-7,8- + 3 Orthophosphate R04621 V 3.6.1.- 2-Amino-4-hydroxy-6-(D-erythro-1,2,3trihydroxypropyl)-7,8- + Orthophosphate <=> Dihydroneopterin phosphate + H2O YES insecure R04638 V 3.6.1.- 2-Amino-4-hydroxy-6-(erythro-1,2,3trihydroxypropyl) + H2O <=> Dihydroneopterin phosphate + Pyrophosphate YES insecure R04639 V 2-Amino-4-hydroxy-6-(erythro-1,2,3trihydroxypropyl) + H2O <=> 3.5.4.16 2,5-Diamino-6-(5'-triphosphoryl-3',4'trihydroxy-2'-oxopentyl)- R05046 V 3.5.4.16 R05048 V 2,5-Diaminopyrimidine nucleoside 3.5.4.16 triphosphate <=> 2,5-Diamino-6-(5'-triphosphoryl-3',4'- Formamidopyrimidine nucleoside triphosphate + H2O <=> 2,5-Diaminopyrimidine nucleoside triphosphate + Formate YES OE5192R insecure 17032654 alternative pathway or enzyme genes for folB and folK likely; 17497938 17032654 alternative pathway or enzyme genes for folB and folK likely; 17497938 YES OE3673F insecure no GTP cyclohydrolase I (folE) in haloarchaea except on H. marismortui plasmid (pNG7382); new class of 17032654 GTP cyclohydrolase (MptA-type) is probably involved in folate/pterine synthesis in archaea; MptA results 17497938 in different cyclic phosphate product; alternative enzyme genes for folB and folK likely; YES OE3673F insecure no GTP cyclohydrolase I (folE) in haloarchaea except on H. marismortui plasmid (pNG7382); new class of 17032654 GTP cyclohydrolase (MptA-type) is probably involved in folate/pterine synthesis in archaea; MptA results 17497938 in different cyclic phosphate product; alternative enzyme genes for folB and folK likely; YES OE3673F insecure no GTP cyclohydrolase I (folE) in haloarchaea except on H. marismortui plasmid (pNG7382); new class of 17032654 GTP cyclohydrolase (MptA-type) is probably involved in folate/pterine synthesis in archaea; MptA results 17497938 in different cyclic phosphate product; alternative enzyme genes for folB and folK likely; 43 trihydroxy-2'-oxopentyl)- R05553 V 4-amino-4-deoxychorismate <=> 4.1.3.38 4-Aminobenzoate + Pyruvate YES OE1574F insecure pabABC clustered; aminodeoxychorismate synthase (EC 6.3.5.8, pabAB) fomerly assigned as anthranilate synthase; pabA (OE1570F) presumably nonfunctional in strain R1 due to an interruption by an ISH 15182204 element; p-aminbenzoate might be synthesized from 3-dehydroquinate and not from chorismate in archaea (PMID:15182204); Biosynthesis of flavin nucleotides react_id subsystem EC-No reaction status genes references comment R00066 V 2.5.1.9 2 6,7-Dimethyl-8-(1-D-ribityl)lumazine <=> Riboflavin + 4-(1-D-Ribitylamino)-5-amino2,6-dihydroxypyrimidine YES secure first steps in riboflavin synthesis differ in haloarchaea (no ribAD); GTP cyclohydrolase III (EC 3.5.4.29, OE2472F) instead of GTP cyclohydrolase II (EC 2.5.4.25, ribA) is probably involved in OE1946R 12475257 riboflavin/coenzyme F420 synthesis in archaea; GTP cyclohydrolase III does not release formate, but OE4683F does hydrolyse diphosphate from GTP to phosphate (R07306); ribBCEG present in haloarchaea, e.g. encoding riboflavin synthase (ribCE); R00160 V 3.6.1.9 3.6.1.18 FAD + H2O <=> AMP + FMN NO possible - R00161 V 2.7.7.2 ATP + FMN <=> Pyrophosphate + FAD NO possible - R00425 V 3.5.4.25 GTP + 3 H2O <=> Formate + 2,5-Diamino-6-hydroxy-4-(5'phosphoribosylamino)-pyrimidine + Pyrophosphate YES secure first steps in riboflavin synthesis differ in haloarchaea (no ribAD); GTP cyclohydrolase III (EC 3.5.4.29, OE2472F) instead of GTP cyclohydrolase II (EC 2.5.4.25, ribA) is probably involved in OE2472F 12475257 riboflavin/coenzyme F420 synthesis in archaea; GTP cyclohydrolase III does not release formate, but does hydrolyse diphosphate from GTP to phosphate (R07306); ribBCEG present in haloarchaea, e.g. encoding riboflavin synthase (ribCE); R00548 V 3.1.3.2 FMN + H2O <=> Riboflavin + Orthophosphate YES likely OE2782F R00549 V 2.7.1.26 ATP + Riboflavin <=> ADP + FMN NO possible - R01734 V - Dimethylbenzimidazole <=> Riboflavin YES likely OE2364R 16537439 R03458 V 5-Amino-6-(5'-phosphoribitylamino)uracil + NADP+ <=> 1.1.1.193 5-Amino-6-(5'-phosphoribosylamino)uracil + NADPH YES secure first steps in riboflavin synthesis differ in haloarchaea (no ribAD); GTP cyclohydrolase III (EC 3.5.4.29, OE2472F) instead of GTP cyclohydrolase II (EC 2.5.4.25, ribA) is probably involved in OE2802F 12475257 riboflavin/coenzyme F420 synthesis in archaea; GTP cyclohydrolase III does not release formate, but does hydrolyse diphosphate from GTP to phosphate (R07306); ribBCEG present in haloarchaea, e.g. encoding riboflavin synthase (ribCE); R03459 V 3.5.4.26 2,5-Diamino-6-hydroxy-4-(5'phosphoribosylamino)-pyrimidine + H2O <=> NO 5-Amino-6-(5'-phosphoribosylamino)uracil + questionable NH3 R04457 V 2.5.1.9 4-(1-D-Ribitylamino)-5-amino-2,6dihydroxypyrimidine + 3,4-Dihydroxy-2butanone 4-phosphate <=> YES secure reaction should be updated: FMN <=> dimethylbenzimidazole + erythrose-4P; reaction catalyzed by BluB; distant homolog found in H. salinarum; first steps in riboflavin synthesis differ in haloarchaea (no ribAD); GTP cyclohydrolase III (EC 3.5.4.29, OE2472F) instead of GTP cyclohydrolase II (EC 2.5.4.25, ribA) is probably involved in 12475257 riboflavin/coenzyme F420 synthesis in archaea; GTP cyclohydrolase III does not release formate, but does hydrolyse diphosphate from GTP to phosphate (R07306); ribBCEG present in haloarchaea, e.g. encoding riboflavin synthase (ribCE); first steps in riboflavin synthesis differ in haloarchaea (no ribAD); GTP cyclohydrolase III (EC OE1946R 12475257 3.5.4.29, OE2472F) instead of GTP cyclohydrolase II (EC 2.5.4.25, ribA) is probably involved in OE4683F riboflavin/coenzyme F420 synthesis in archaea; GTP cyclohydrolase III does not release formate, but 44 6,7-Dimethyl-8-(1-D-ribityl)lumazine + 2 H2O + Orthophosphate R07280 V R07281 V R07306 V does hydrolyse diphosphate from GTP to phosphate (R07306); ribBCEG present in haloarchaea, e.g. encoding riboflavin synthase (ribCE); first steps in riboflavin synthesis differ in haloarchaea (no ribAD); GTP cyclohydrolase III (EC 3.5.4.29, OE2472F) instead of GTP cyclohydrolase II (EC 2.5.4.25, ribA) is probably involved in 12475257 riboflavin/coenzyme F420 synthesis in archaea; GTP cyclohydrolase III does not release formate, but does hydrolyse diphosphate from GTP to phosphate (R07306); ribBCEG present in haloarchaea, e.g. encoding riboflavin synthase (ribCE); 3.1.3.- 5-Amino-6-(5'-phosphoribitylamino)uracil + H2O <=> 4-(1-D-Ribitylamino)-5-amino-2,6dihydroxypyrimidine + Orthophosphate - D-Ribulose 5-phosphate <=> 3,4-Dihydroxy-2-butanone 4-phosphate + Formate YES secure first steps in riboflavin synthesis differ in haloarchaea (no ribAD); GTP cyclohydrolase III (EC 3.5.4.29, OE2472F) instead of GTP cyclohydrolase II (EC 2.5.4.25, ribA) is probably involved in OE3963R 12475257 riboflavin/coenzyme F420 synthesis in archaea; GTP cyclohydrolase III does not release formate, but does hydrolyse diphosphate from GTP to phosphate (R07306); ribBCEG present in haloarchaea, e.g. encoding riboflavin synthase (ribCE); 3.5.4.29 GTP + 3 H2O <=> 2-Amino-5-formylamino-6-(5phosphoribosylamino)pyrimidin-4(3H)-one + 2 Orthophosphate YES likely first steps in riboflavin synthesis differ in haloarchaea (no ribAD); GTP cyclohydrolase III (EC 3.5.4.29, OE2472F) instead of GTP cyclohydrolase II (EC 2.5.4.25, ribA) is probably involved in OE2472F 12475257 riboflavin/coenzyme F420 synthesis in archaea; GTP cyclohydrolase III does not release formate, but does hydrolyse diphosphate from GTP to phosphate (R07306); ribBCEG present in haloarchaea, e.g. encoding riboflavin synthase (ribCE); YES insecure - Biosynthesis of nicotinamide nucleotides react_id subsystem EC-No reaction status genes references R00103 V 3.6.1.9 NAD+ + H2O <=> 3.6.1.22 AMP + Nicotinamide D-ribonucleotide NO possible R00137 V 2.7.7.1 ATP + Nicotinamide D-ribonucleotide <=> 2.7.7.18 Pyrophosphate + NAD+ YES secure OE1462R - R00189 V 6.3.1.5 ATP + Deamino-NAD+ + NH3 <=> AMP + Pyrophosphate + NAD+ YES secure OE3843F R00257 V 6.3.5.1 ATP + Deamino-NAD+ + L-Glutamine + H2O <=> AMP + Pyrophosphate + NAD+ + L-Glutamate YES secure OE3843F R00357 V 1.4.3.16 L-Aspartate + H2O + Oxygen <=> Oxaloacetate + NH3 + H2O2 YES secure OE3646F R00481 V 1.4.3.16 L-Aspartate + Oxygen <=> Iminoaspartate + H2O2 YES secure OE3646F R03004 V 3.6.1.9 Deamino-NAD+ + H2O <=> 3.6.1.22 AMP + Nicotinate D-ribonucleotide NO possible R03005 V 2.7.7.1 ATP + Nicotinate D-ribonucleotide <=> 2.7.7.18 Pyrophosphate + Deamino-NAD+ YES secure OE1462R - R03348 V Nicotinate D-ribonucleotide + Pyrophosphate + CO2 <=> 2.4.2.19 Pyridine-2,3-dicarboxylate + 5-Phospho-alpha-D-ribose 1diphosphate YES secure OE3648F R04292 V - YES OE3644F Pyridine-2,3-dicarboxylate + 2 H2O + Orthophosphate <=> comment EC 2.7.7.1 secure; EC 2.7.7.18 (nadD) unlikely since no homolog in Hasal (and gap_arch); EC 2.7.7.1 secure; EC 2.7.7.18 (nadD) unlikely since no homolog in Hasal (and gap_arch); 45 Iminoaspartate + Glycerone phosphate secure Coenzyme A biosynthesis react_id subsystem EC-No reaction status YES likely genes references comment R00130 V 2.7.1.24 ATP + Dephospho-CoA <=> ADP + CoA R00489 A 4.1.1.11 4.1.1.15 L-Aspartate <=> beta-Alanine + CO2 NO questionable 15715981 OE1498R is homologous to novel archaeal Tyr decarboxylase; OE1498R was formerly a Glu decarboxylase candidate; R01211 V 1.1.1.84 NADH + (R)-3,3-Dimethylmalate + NAD+ <=> 3-Methyl-2-oxobutanoate + CO2 + NADH NO unlikely - - no enzyme genes known yet; R01214 A 2.6.1.42 L-Valine + 2-Oxoglutarate <=> 3-Methyl-2-oxobutanoate + L-Glutamate YES secure OE3959R - R01226 V 2.1.2.11 5,10-Methylenetetrahydrofolate + 3-Methyl-2oxobutanoate + H2O <=> Tetrahydrofolate + 2-Dehydropantoate YES secure OE3119R R02471 V 1.1.1.106 (R)-Pantoate + NAD+ <=> (R)-4-Dehydropantoate + NADH NO unlikely - R02472 V 1.1.1.169 (R)-Pantoate + NADP+ <=> 2-Dehydropantoate + NADPH YES secure OE2078R R02473 V 6.3.2.1 ATP + (R)-Pantoate + beta-Alanine <=> AMP + Pyrophosphate + Pantothenate YES insecure - R02474 V 3.5.1.22 Pantothenate + H2O <=> (R)-Pantoate + beta-Alanine NO unlikely - R02971 V 2.7.1.33 2.7.1.34 ATP + Pantetheine <=> ADP + Pantetheine 4'-phosphate YES insecure - R02972 V 4.1.1.30 N-((R)-Pantothenoyl)-L-cysteine <=> Pantetheine + CO2 NO unlikely - R03018 V 2.7.1.33 ATP + Pantothenate <=> ADP + D-4'-Phosphopantothenate YES insecure - R03035 V 2.7.7.3 ATP + Pantetheine 4'-phosphate <=> Pyrophosphate + Dephospho-CoA YES likely OE2992R R03036 V 3.6.1.9 Dephospho-CoA + H2O <=> Pantetheine 4'-phosphate + AMP NO possible - R03198 V 1.2.1.33 (R)-4-Dehydropantoate + NAD+ + H2O <=> (R)-3,3-Dimethylmalate + NADH NO unlikely - R03269 V 4.1.1.36 (R)-4'-Phosphopantothenoyl-L-cysteine <=> Pantetheine 4'-phosphate + CO2 YES likely OE1856R R04230 V 6.3.2.5 ATP + D-4'-Phosphopantothenate + L-Cysteine <=> YES OE1856R OE4442F 2.6.1.42 required for Val, Leu, Ile degradation; no enzymes for synth. pathways found; no_seq for 2.6.1.6.; - no enzyme genes known yet; - no enzyme genes known yet; - no enzyme genes known yet; 46 ADP + Orthophosphate + (R)-4'-Phosphopantothenoyl-Lcysteine likely R04231 V 6.3.2.5 CTP + D-4'-Phosphopantothenate + L-Cysteine <=> CMP + Pyrophosphate + (R)-4'-Phosphopantothenoyl-Lcysteine YES likely OE1856R R04233 V 6.3.2.5 CTP + D-4'-Phosphopantothenate + L-Cysteine <=> CDP + Orthophosphate + (R)-4'-Phosphopantothenoyl-Lcysteine YES likely OE1856R R04391 V 2.7.1.33 ATP + N-((R)-Pantothenoyl)-L-cysteine <=> ADP + (R)-4'-Phosphopantothenoyl-L-cysteine YES insecure - Menaquinone biosynthesis react_id subsystem EC-No reaction status genes NO unlikely references comment R00071 V - 2 5-Hydroxy-2-polyprenylphenol <=> Oxygen + 2 2-Polyprenylphenol R00622 V 2.5.1.64 2-Oxoglutarate + Thiamin diphosphate <=> Succinate semialdehyde-thiamin diphosphate anion + CO2 YES secure R01302 V 4.1.3.40 4-Hydroxybenzoate + Pyruvate <=> Chorismate NO unlikely R01717 V 5.4.4.2 Chorismate <=> Isochorismate YES secure R02162 V - Ubiquinol + 3 S-Adenosyl-L-homocysteine <=> 5-Hydroxy-2-polyprenylphenol + Oxygen + 3 S-Adenosyl-Lmethionine NO unlikely - no ubi/coq cluster found in HS; R02163 V 1.6.5.3 Ubiquinol + NAD+ <=> Ubiquinone + NADH NO unlikely - no ubi/coq cluster found in HS; menaquinol to menaquinone likely reaction in Hasal respiratory chain (complex III); pet cluster found; R02166 V 1.6.5.3 Ubiquinol <=> Ubiquinone + 2 H+ NO unlikely - no ubi/coq cluster found in HS; menaquinol to menaquinone likely reaction in Hasal respiratory chain (complex III); pet cluster found; R02964 V 1.6.5.- Menaquinone + 2 H+ <=> Menaquinol OE1872R YES OE1874R insecure OE1876R menaquinol to menaquinone likely reaction in Hasal respiratory chain (complex III); pet cluster found; R04030 V 6.2.1.26 ATP + 2-Succinylbenzoate + CoA <=> AMP + Pyrophosphate + 2-Succinylbenzoyl-CoA YES secure OE2555R - menaquinones found in HS (Oesterhelt76); men cluster found; enzymes for all-trans long chain isoprenoids identified; R04031 V 4.2.1.- 2-Succinylbenzoate + H2O <=> 2-Succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate YES secure OE2558R - menaquinones found in HS (Oesterhelt76); men cluster found; enzymes for all-trans long chain isoprenoids identified; R04150 V 4.1.3.36 2-Succinylbenzoyl-CoA <=> 1,4-Dihydroxy-2-naphthoate + CoA YES secure OE2561R - menaquinones found in HS (Oesterhelt76); men cluster found; enzymes for all-trans long chain isoprenoids identified; R04985 V - 2-Polyprenylphenol <=> 4-Hydroxy-3-polyprenylbenzoate NO unlikely - OE2563R - OE2566R - - no ubi/coq cluster found in HS; menaquinones found in HS (Oesterhelt76); men cluster found; enzymes for all-trans long chain isoprenoids identified; no ubi/coq cluster found in HS; menaquinones found in HS (Oesterhelt76); men cluster found; enzymes for all-trans long chain isoprenoids identified; no ubi/coq cluster found in HS; 47 R04992 V 2.5.1.64 Succinate semialdehyde-thiamin diphosphate anion + Isochorismate <=> 2-Succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate + Thiamin diphosphate + Pyruvate YES secure OE2563R - menaquinones found in HS (Oesterhelt76); men cluster found; enzymes for all-trans long chain isoprenoids identified; R04993 V 2.1.1.- 2-Demethylmenaquinone + S-Adenosyl-L-methionine <=> Menaquinol + S-Adenosyl-L-homocysteine YES OE3994F insecure menaquinones found in HS (Oesterhelt76); men cluster found; enzymes for all-trans long chain isoprenoids identified; R05617 V 2.5.1.- 1,4-Dihydroxy-2-naphthoate + all-trans-Octaprenyl diphosphate <=> 2-Demethylmenaquinone + Pyrophosphate + CO2 YES secure menaquinones found in HS (Oesterhelt76); men cluster found; enzymes for all-trans long chain isoprenoids identified; OE2559R - Biotin biosynthesis react_id subsystem EC-No reaction status genes references comment R00742 V 6.4.1.2 ATP + Acetyl-CoA + HCO3- <=> ADP + Orthophosphate + Malonyl-CoA YES OE3175F insecure OE1939F propionyl-CoA carboxylase (EC 6.4.1.3) (OE3175F, OE1939F) might also function as acetyl-CoA carboxylase (EC 6.4.1.2); R01078 V 2.8.1.6 Dethiobiotin + Sulfur <=> Biotin NO unlikely - no bio genes in Hasal in contrast to Napha; initial steps of biotin synth unknown; probably 3 malonoyl-CoA as precurser of pimeloyl-CoA; R03182 V 6.3.3.3 ATP + 7,8-Diaminononanoate + CO2 <=> ADP + Orthophosphate + Dethiobiotin NO unlikely - no bio genes in Hasal in contrast to Napha; initial steps of biotin synth unknown; probably 3 malonoyl-CoA as precurser of pimeloyl-CoA; R03209 V 6.2.1.14 ATP + 6-Carboxyhexanoate + CoA <=> AMP + Pyrophosphate + 6-Carboxyhexanoyl-CoA NO unlikely R03210 V 2.3.1.47 6-Carboxyhexanoyl-CoA + L-Alanine <=> 8-Amino-7-oxononanoate + CoA + CO2 NO unlikely - no bio genes in Hasal in contrast to Napha; initial steps of biotin synth unknown; probably 3 malonoyl-CoA as precurser of pimeloyl-CoA; R03231 V S-Adenosyl-L-methionine + 8-Amino-7oxononanoate <=> 2.6.1.62 S-Adenosyl-4-methylthio-2-oxobutanoate + 7,8Diaminononanoate NO unlikely - no bio genes in Hasal in contrast to Napha; initial steps of biotin synth unknown; probably 3 malonoyl-CoA as precurser of pimeloyl-CoA; R04386 V 6.4.1.2 Acetyl-CoA + Carboxybiotin-carboxyl-carrier protein <=> Malonyl-CoA + Holo-[carboxylase] YES OE3175F insecure OE1939F propionyl-CoA carboxylase (EC 6.4.1.3) (OE3175F, OE1939F) might also function as acetyl-CoA carboxylase (EC 6.4.1.2); R10006 V - 3 Malonyl-CoA <=> 6-Carboxyhexanoyl-CoA + 2 CoA + 2 CO2 NO unlikely no bio genes in Hasal in contrast to Napha; initial steps of biotin synth unknown; probably 3 malonoyl-CoA as precurser of pimeloyl-CoA; - Thiamin biosynthesis react_id subsystem EC-No reaction R00615 V Thiamin diphosphate + H2O <=> 3.6.1.15 Thiamin monophosphate + Orthophosphate R00617 V 2.7.4.16 ATP + Thiamin monophosphate <=> ADP + Thiamin diphosphate status genes references YES secure OE3863R YES likely OE3818F - comment initial steps of thiamine synthesis unknown; many non-orthologous enzymes in thi biosynthesis pathway; some thi genes present in N. pharaonis but absent in H. salinarum, e.g. TU thiEM 48 (NP4052A/NP4054A); R03223 V 2.5.1.3 2-Methyl-4-amino-5-hydroxymethylpyrimidine diphosphate + 4-Methyl-5-(2-phosphoethyl)-thiazole <=> Pyrophosphate + Thiamin monophosphate R03471 V 2.7.1.49 ATP + 4-Amino-5-hydroxymethyl-2methylpyrimidine <=> ADP + 4-Amino-2-methyl-5phosphomethylpyrimidine YES insecure R03472 V - 4-Amino-5-hydroxymethyl-2-methylpyrimidine <=> Aminoimidazole ribotide YES likely R04448 V 2.7.1.50 ATP + 5-(2-Hydroxyethyl)-4-methylthiazole <=> ADP + 4-Methyl-5-(2-phosphoethyl)-thiazole YES insecure R04509 V 2.7.4.7 ATP + 4-Amino-2-methyl-5phosphomethylpyrimidine <=> ADP + 2-Methyl-4-amino-5hydroxymethylpyrimidine diphosphate YES likely YES likely thiN is the non-orthologous variant of canonical thiE (PMID:12794638); only thiN (OE1385F, OE1385F 12794638 OE4654F fused to thiD) found in H. salinarum; both, thiE (NP4054A) and thiN (NP0546A fused to OE4654F thiD, NP5168A) are present in N. pharaonis; - initial steps of thiamine synthesis unknown; many non-orthologous enzymes in thi biosynthesis pathway; some thi genes present in N. pharaonis but absent in H. salinarum, e.g. TU thiEM (NP4052A/NP4054A); tenA is the non-orthologous variant of canonical thiC (PMID:12794638); only thiC (OE2057F) OE2057F 12794638 found in H. salinarum; both, thiC (NP2210A) and tenA (NP4080A, NP4082A) are present in N. pharaonis; - initial steps of thiamine synthesis unknown; many non-orthologous enzymes in thi biosynthesis pathway; some thi genes present in N. pharaonis but absent in H. salinarum, e.g. TU thiEM (NP4052A/NP4054A); OE4654F - initial steps of thiamine synthesis unknown; many non-orthologous enzymes in thi biosynthesis pathway; some thi genes present in N. pharaonis but absent in H. salinarum, e.g. TU thiEM (NP4052A/NP4054A); Pyridoxal 5-phosphate biosynthesis react_id subsystem EC-No reaction status genes references comment R00174 V 2.7.1.35 ATP + Pyridoxal <=> ADP + Pyridoxal phosphate NO unlikely archaea presumably synthesize pyridoxal 5-phosphate by novel pyridoxal 5-phosphate synthesis enzymes 16030023 (pdxS/pdxT, OE3524F, OE4644R) like B. subtilis (PMID:16030023); canonical pdx genes absent in archaea; R00277 V 1.4.3.5 Pyridoxamine phosphate + H2O + Oxygen <=> Pyridoxal phosphate + NH3 + H2O2 NO unlikely 16030023 archaea presumably synthesize pyridoxal 5-phosphate by novel pyridoxal 5-phosphate synthesis enzymes (pdxS/pdxT, OE3524F, OE4644R) like B. subtilis (PMID:16030023); canonical pdx genes absent in archaea; R00278 V 1.4.3.5 Pyridoxine phosphate + Oxygen <=> H2O2 + Pyridoxal phosphate NO unlikely 16030023 archaea presumably synthesize pyridoxal 5-phosphate by novel pyridoxal 5-phosphate synthesis enzymes (pdxS/pdxT, OE3524F, OE4644R) like B. subtilis (PMID:16030023); canonical pdx genes absent in archaea; R01710 V 1.4.3.5 Pyridoxamine + H2O + Oxygen <=> Pyridoxal + NH3 + H2O2 NO unlikely 16030023 archaea presumably synthesize pyridoxal 5-phosphate by novel pyridoxal 5-phosphate synthesis enzymes (pdxS/pdxT, OE3524F, OE4644R) like B. subtilis (PMID:16030023); canonical pdx genes absent in archaea; R01711 V 1.4.3.5 Pyridoxine + Oxygen <=> Pyridoxal + H2O2 NO unlikely 16030023 archaea presumably synthesize pyridoxal 5-phosphate by novel pyridoxal 5-phosphate synthesis enzymes (pdxS/pdxT, OE3524F, OE4644R) like B. subtilis (PMID:16030023); canonical pdx genes absent in archaea; R01825 V 1.2.1.- D-Erythrose 4-phosphate + NAD+ + H2O <=> 4-Phospho-D-erythronate + NADH + H+ NO unlikely 16030023 archaea presumably synthesize pyridoxal 5-phosphate by novel pyridoxal 5-phosphate synthesis enzymes (pdxS/pdxT, OE3524F, OE4644R) like B. subtilis (PMID:16030023); canonical pdx genes absent in archaea; R01909 V 2.7.1.35 ATP + Pyridoxine <=> ADP + Pyridoxine phosphate NO unlikely 16030023 archaea presumably synthesize pyridoxal 5-phosphate by novel pyridoxal 5-phosphate synthesis enzymes (pdxS/pdxT, OE3524F, OE4644R) like B. subtilis (PMID:16030023); canonical pdx genes absent in archaea; R02493 V 2.7.1.35 ATP + Pyridoxamine <=> ADP + Pyridoxamine phosphate NO unlikely 16030023 archaea presumably synthesize pyridoxal 5-phosphate by novel pyridoxal 5-phosphate synthesis enzymes (pdxS/pdxT, OE3524F, OE4644R) like B. subtilis (PMID:16030023); canonical pdx genes absent in archaea; 49 R04210 V 1.1.1.1.1.1.95 4-Phospho-D-erythronate + NAD+ <=> 2-Oxo-3-hydroxy-4-phosphobutanoate + NADH R05085 V 2.6.1.52 O-Phospho-4-hydroxy-L-threonine + 2Oxoglutarate <=> YES archaea presumably synthesize pyridoxal 5-phosphate by novel pyridoxal 5-phosphate synthesis enzymes OE4391F 16030023 2-Oxo-3-hydroxy-4-phosphobutanoate + L- insecure (pdxS/pdxT, OE3524F, OE4644R) like B. subtilis (PMID:16030023); canonical pdx genes absent in archaea; Glutamate R05837 V O-Phospho-4-hydroxy-L-threonine + NAD+ <=> 1.1.1.262 3-Amino-2-oxopropyl phosphate + NADH + H+ + CO2 NO unlikely 16030023 archaea presumably synthesize pyridoxal 5-phosphate by novel pyridoxal 5-phosphate synthesis enzymes (pdxS/pdxT, OE3524F, OE4644R) like B. subtilis (PMID:16030023); canonical pdx genes absent in archaea; R05838 V 3-Amino-2-oxopropyl phosphate + 1Deoxy-D-xylulose 5-phosphate <=> Pyridoxine phosphate + Orthophosphate + 2 H2O NO unlikely 16030023 archaea presumably synthesize pyridoxal 5-phosphate by novel pyridoxal 5-phosphate synthesis enzymes (pdxS/pdxT, OE3524F, OE4644R) like B. subtilis (PMID:16030023); canonical pdx genes absent in archaea; - YES archaea presumably synthesize pyridoxal 5-phosphate by novel pyridoxal 5-phosphate synthesis enzymes OE4408F 16030023 insecure (pdxS/pdxT, OE3524F, OE4644R) like B. subtilis (PMID:16030023); canonical pdx genes absent in archaea; 50
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