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1 Microbial Metabolism Production and Regulation of Primary and Secondary Metabolites Ching-Tsan Huang (黃慶璨) Office: Agronomy Hall, Room 111 Tel: (02) 33664454 E-mail: [email protected] 2 Products of Microbiology 3 Primary Metabolites Small molecules of living cells Intermediates or end products of the pathway Related to synthesis of microbial cells in the growth phase Include alcohols, amino acids, nucleotides, organic acids, polyols, vitamins, and enzymes 4 Secondary Metabolites Accumulate following active growth Have no direct relationship to synthesis of cell material and natural growth Include antibiotics and toxins 5 Relation between 1o and 2o metabolic pathway Primary metabolic pathway for the synthesis of aromatic amino acids The secondary metabolite antibiotics containing aromatic rings. 6 Regulation Mechanisms Central Dogma 7 Modification of Gene Expression allows for overproduction of a product, production of more than one product by the same organism, or synthesis of modified products Pathway architecture analysis, design, and modification of biochemical pathways to increase process efficiency Metabolic pathway engineering intentional alteration of metabolic pathway by inactivation of specific genes Metabolic control engineering alteration of control mechanisms of specific genes 8 Feedback inhibition of enzyme activity 9 Specific Feedback Inhibition 10 Enzyme Inhibition by Allosteric Effector 11 Negative Control of Transcription Repression Inactive Active 12 Negative Control of Transcription Induction Active Inactive 13 Positive Control of Enzyme Induction Inactive Active 14 Positive Control of Transcription 15 Catabolite Repression Occurs when operon is under control of catabolite other than initial substrate Allows preferential use of one carbon source over another 16 Transcription of trp operon by attenuation 17 Transcription of trp operon by attenuation 18 Two-Component System 19 Production of Vinegar 20 21 Citric Acid Fermentation 22 Antibiotics Requires precise control of nutrients Final product can be modified to yield a variety of semisynthetic penicillins 23 Biosynthetic Pathway of Penicillin ACV synthetase IPN synthetase Acyltransferase 24 Industrial Production of Penicillins