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5.451 F2005
Alkaloid Biosynthesis:
Nitrogen containing compounds
CO2Me
Me
Amino Acids:
Ornithine
Lysine
Tyrosine
Tryptophan
Starting materials:
Amino acids and nucleic acids
N
O
cocaine
NH3
O
H3N
CO2
N
H Me
Purine
ornithine
N
nicotine
NH2
O
H3C
CH3
N
N
N
O
-O P O
O-
N
N
CH3
O
N
NH3
N
Me
N
N
O
O
H3N
CO2
OH OH
caffeine
purine
HO
OH
pseudopelletierine
O
O
H
H
NCH3
HO
morphine
tyrosine
OH
H
CO2
NH3
NMe
H
NH3
CO2
lysine
HN
ergot (fungus)
rebeccamycin
staurosporine
N
H
tryptophan
5.451 F2005
Alkaloid Biosynthesis:
Purine Derived Products: Caffeine
Figure removed due to copyright reasons.
Please see Figure 4 in Trends Plant Sci 6 (2001): 407.
T
5.451 F2005
Alkaloid Biosynthesis:
Purine Derived Products: Caffeine
Genetically engineered decaf coffee
70% reduction in caffeine content by using RNAi of theobromine synthase
otherwise normal phenotype
Nature (2003) 423, 823
Recently discovered natural variant deficient in caffeine synthase
Nature (2004) 429, 826.
Promoter of the 3 methyl transferases recently discovered
J. Biotech. (2005) 119, 20-25.
5.451 F2005
Alkaloid Biosynthesis:
Ornithine and Lysine Derived Products
Me
H
N
N
H Me
N
tropanes
H2N
NH2
putrescine (via ornithine)
2 acetates
Me
N
nicotine
H2N
pyrrolizidine
NH2
putrescine (via ornithine)
nicotinic acid
homospermidine
(via 2 putrescines)
N
pseudopelletierine
cadaverine (via lysine)
2 acetates
N
N
quinolizidines
indolizidines
2 cadaverines
pipecolic acid (via lysine)
1 acetate
5.451 F2005
Alkaloid Biosynthesis:
Ornithine Derived Products
N
H Me
N
H
N
pyrrolidines
nicotine
H+
O
CO2H
H-
N
H
N
H Me
OH
CO2
N
N
H
H
N
+
H
NADP+
nicotinic acid
B3 (niacin)
N
Me
N
H Me
5.451 F2005
Alkaloid Biosynthesis:
Ornithine Derived Products
H
N
pyrrolizidine
5.451 F2005
Alkaloid Biosynthesis:
Ornithine Derived Products
H
Origin of a secondary metabolic pathway?
Found only in angiosperms
N
pyrrolizidine
H2N
NH2
+
H2N
HS synthase
N
H
NH2
H2N
NH2
N
H
homosperrmidine
putrescine
spermidine
DH synthase
NH2
E
+
H2N
N
H
NH2
H
N
NH2
E
deoxyhypusine
synthase
deoxyhypusine
E = elF5A
lysine of transcription factor
H
N
OH
E
NH2
hypusine
PNAS (1999) 96, p. 14779
5.451 F2005
Alkaloid Biosynthesis:
Lysine Derived Products
NH2
NH2
N
H
piperidines
H3N
CO2
ornithine
H3N
CO2
lysine
5.451 F2005
Alkaloid Biosynthesis:
Lysine Derived Products
N
quinolizidines
H2N
H
NH2
CHO
H
N
H2N
CHO
CHO
H
NH
NH2
CHO
N
N
NH
H
N
H
NH
NH2
H2N
NH2
OHC
H
CHO
NH
CHO
H2N
NH
H2N
N
H2N
OHC
N
H
N
H
NH2
NH2
5.451 F2005
Alkaloid Biosynthesis:
Lysine Derived Products
N
indolizidines
acetate
pipecolic acid
H3N
NH2
H2N
H
CO2
CO2
CO2H
O
O
H
SCoA
NH
NH
O
H
N
OMe
HO
cyclohexyl
CoA
shikimic
acid
O
OH
MeO
O
polyketide/peptide
rapamycin
O
N
O
O
O MeO
OH H
O
O
5.451 F2005
Alkaloid Biosynthesis:
Ornithine Derived Products
Source of alkaloids
arthropod eats plant;
or ant or symbiontof ant makes alkaloid
vertebrate (frog) eats ant
Figure removed due to copyright reasons.
alkaloids found in ants and frogs
See Figure 1 in PNAS 101 (2004): 8045.
Figure removed due to copyright reasons.
after injestion, can be derivatized by frog to make more poisonous
See Figure 1 in PNAS 100 (2003): 11092.
5.451 F2005
Alkaloid Biosynthesis:
Ornithine Derived Products
Chemical Defense
Figures removed due to copyright reasons.
5.451 F2005
Alkaloid Biosynthesis:
Ornithine Derived Products
Removed due to copyright reasons.
5.451 F2005
Alkaloid Biosynthesis:
Ornithine Derived Products
Outwitting the Chemical DefenseDetoxification by oxidation
H
N
pyrrolizidine
CHO
H
N
O
detoxification
Figure removed due to copyright reasons.
Please see Figure 1 in PNAS 99 (2002): 6085.