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Amino Acids:OrnithineLysineTyrosineTryptophan
Purine
Starting materials:Amino acids and nucleic acids
NMe
HN
OHO
H
H
N
N N
N
O
O
CH3
CH3
H3C
NMe O
CO2Me
O
pseudopelletierine
nicotineN
NMeH
caffeine
ergot
O
NCH3
HO
HO
HH
morphine
CO2
NH3
OH
NH
NH3
CO2
N
NN
N
NH2
O
OHOH
OP-O
O-
O
NH3
CO2
H3N
CO2
H3N
NH3
NMe
O
cocaine
ornithine
purine
tyrosine
lysine
tryptophan
5.451 F2005Alkaloid Biosynthesis:Nitrogen containing compounds
(fungus)
rebeccamycinstaurosporine
5.451 F2005Alkaloid Biosynthesis:Purine Derived Products: Caffeine
T
Figure removed due to copyright reasons. Please see Figure 4 in Trends Plant Sci 6 (2001): 407.
5.451 F2005Alkaloid 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.
pyrrolizidine
5.451 F2005Alkaloid Biosynthesis:Ornithine and Lysine Derived Products
N
H
homospermidine(via 2 putrescines)
tropanes
NMe
nicotineN
NMeH
quinolizidines
N
indolizidines
N
NH2H2N
putrescine (via ornithine)2 acetates
NH2H2N
putrescine (via ornithine)nicotinic acid
NMe
pseudopelletierine
cadaverine (via lysine)2 acetates
2 cadaverines pipecolic acid (via lysine)1 acetate
pyrrolidines nicotine
N
NMeHN
H
5.451 F2005 Alkaloid Biosynthesis:Ornithine Derived Products
N
CO2H
N
OH
O
NH N
H
H
NMeH
NMeH
NMe
H-
H+
H+
NADP+
CO2
nicotinic acid
B3 (niacin)
pyrrolizidine
5.451 F2005 Alkaloid Biosynthesis:Ornithine Derived Products
N
H
pyrrolizidine
5.451 F2005 Alkaloid Biosynthesis:Ornithine Derived Products
N
H
PNAS (1999) 96, p. 14779
Origin of a secondary metabolic pathway?Found only in angiosperms
NH
H2NNH2
H2N NH2NH
H2NNH2+
NH2E
NH
H2NNH2+
HN
E NH2
E = elF5A
HN
E NH2
OH
hypusine
deoxyhypusine
spermidine
lysine of transcription factor
putrescine homosperrmidine
HS synthase
DH synthase
deoxyhypusinesynthase
piperidines ornithine
5.451 F2005 Alkaloid Biosynthesis:Lysine Derived Products
NH
H3N CO2
NH2
H3N CO2
NH2
lysine
quinolizidines
5.451 F2005 Alkaloid Biosynthesis:Lysine Derived Products
N
N
H2N NH2 H2N CHONH NH
NH
NH
HNH
CHOH
NH2
NH
CHOH
CHO
CHOH
NH2H2N
NH
H2N
N
NH2H2N NH2
NH
OHC NH2OHC
N
HCHO
N
H2N
indolizidines
5.451 F2005 Alkaloid Biosynthesis:Lysine Derived Products
N
H3N NH2NH N
CO2
H2N H
CO2 O
CO2H
NH
O O
SCoAH H O
O
O
OH O
MeOO
O
N
HO
MeO
OO
OH H
OMe
pipecolic acid acetate
polyketide/peptiderapamycin
cyclohexylCoA
shikimicacid
5.451 F2005 Alkaloid Biosynthesis:Ornithine Derived Products
Source of alkaloidsarthropod eats plant;or ant or symbiontof ant makes alkaloidvertebrate (frog) eats ant
after injestion, can be derivatized by frog to make more poisonousSee Figure 1 in PNAS 100 (2003): 11092.
alkaloids found in ants and frogsSee Figure 1 in PNAS 101 (2004): 8045.
Figure removed due to copyright reasons.
Figure removed due to copyright reasons.
5.451 F2005 Alkaloid Biosynthesis:Ornithine Derived ProductsChemical Defense
Figures removed due to copyright reasons.
5.451 F2005 Alkaloid Biosynthesis:Ornithine Derived Products
Removed due to copyright reasons.
pyrrolizidine
5.451 F2005 Alkaloid Biosynthesis:Ornithine Derived ProductsOutwitting the Chemical Defense- Detoxification by oxidation
N
H
N
HCHO
O
detoxification
Figure removed due to copyright reasons. Please see Figure 1 in PNAS 99 (2002): 6085.