Professional Documents
Culture Documents
Polysaccharides
Glycosides
Nucleic Acids
phosphoenol
pyruvate Shikimate pathway
Aromatic Compounds
Lignans
Shikimate
aromatic amino acids
pyruvate aliphatic amino acids
Alkaloids
Peptides
CITRIC Penicillins
acetyl ACID
CoA CH3COSCoA CYCLE Cyclic Peptides
CH3COSCoA
-
O2CCH2COSCoA CH3COCH2COSCoA
CH3COSCoA
(3)
CH3COSCoA
Isoprenoids (terpenes,
steroids, carotenoids)
mevalonate
Polyketides, Fatty Acids Prostaglandins, Macrocyclic Antibiotics
(3) Isoprene pathway: Terpenes
(3) Mevalonate Terpenes, Steroids
-- made from 5-carbon units
- C6 compound
that loses CO2
phytane (C20)
to form C5 units
DMAP IPP
Prenyl transferase +
rearranged to form
sesquiterpenes (C15)
Biosynthesis of Sesquiterpenes (C15)
DMAP IPP Geranyl pyrophosphate (C10)
Prenyl transferase +
Prenyl transferase +
13
C NMR spectrum of compound 2, after feeding sea slug with
[2-13C] mevalonate - increased size of peaks shows label incorporation
- allowed researchers to
infer biosynthetic pathway
for these related C-23 and
C-21 terpenes
Biosynthesis of Trichodiene (C15)
Trichodiene
- Precursor (mevalonate) can be labeled at a particular atom with
a stable isotope (13C); fate of label then traced in final product
Biosynthesis of Trichodiene (C15)
Trichodiene
- Biosynthesis proceeds via carbocation intermediates, migration
of 2 methyl groups and a hydrogen
Trichodiene Trichothecenes
Trichodiene is a key precursor of fungal metabolites called
trichothecenes, a major human health problem
- fungal toxins are called mycotoxins
- often present in moldy grain consumed by cattle or people
Winter 1942: thousands of Russians died after eating grains
left in the field over winter, due to the war; grain was infected
with the trichothecene-producing fungus
1981: USA accused Russia of spraying fungal spores in Vietnam,
resulting in foliage contaminated with trichothecenes (false)
Diterpene (C20) Biosynthesis
+
Farnesyl pyrophosphate (C15)
Diterpenes
Gibberellin Biosynthesis
Squalene
other C30 triterpenes
cholesterol (C27)
sex hormones
vitamin D
Cholesterol Biosynthesis
- lose 3 methyl
groups
Vitamin D Biosynthesis
- cholesterol from
liver is transported
to skin
- photochemically
converted into
- vitamin allows uptake vitamin D
of essential calcium
Notes on Terpenes
(1) Oxidation reactions are carried out by the enzyme
cytochrome P450
- activate oxygen to introduce -OH, carboxyl groups
- allow removal of C’s through decarboxylation
Lycopene
- major antioxidant pigment in tomatoes
-carotene
- major accessory pigment in photosynthesis
The highest terpenes (Cbig #)
~ 1 % of plants can synthesize cis-polyisoprenoids, like rubber
H3C
Polysaccharides
Glycosides
Nucleic Acids
phosphoenol
pyruvate Shikimate pathway
Aromatic Compounds
Lignans
Shikimate
aromatic amino acids
pyruvate aliphatic amino acids
Alkaloids
Peptides
CITRIC Penicillins
acetyl ACID
CoA CH3COSCoA CYCLE Cyclic Peptides
CH3COSCoA
-
O2CCH2COSCoA CH3COCH2COSCoA
CH3COSCoA
CH3COSCoA
Isoprenoids (terpenes,
steroids, carotenoids)
mevalonate (4)
Polyketides, Fatty Acids Prostaglandins, Macrocyclic Antibiotics
(4) Polyketide Biosynthesis
H3 C SCoA Erythromycin A
(antibacterial)
Avermectin B1
(antihelminthic)
(4) Polyketide Biosynthesis
(4) Acetate Polyketides:
O
(1) aromatic compounds, usually
with meta placement of -OH’s
Avermectin B1
6-methyl salicylate (antihelminthic)
Polyketide Biosynthesis
Compounds constructed by addition of successive 2-carbon units
O OH
H
-or- -or- H3 C C
H3 C C H3 C C
Polyketide Biosynthesis
Important natural producers of polyketide metabolites:
- fungi (= molds)
- sea slugs
Polyketide Biosynthesis
Actual pathway starts with an acetyl-coA, but then successively
uses malonyl coA, which loses CO2 thus adding C2 units
- analogous to how mevalonate loses CO2 to add C5 units in
terpenoid biosynthesis
…End with 17 ?
Griseofulvin Biosynthesis
Post-cyclization modifications:
(1) addition of methoxy groups
(2) halogenation
Actinorhodin Biosynthesis
Antibiotic from bacterium Streptomyces coelicolor
methylated
afterwards
kalafungin actinorhodin
(an antibiotic
intermediate)
Aflatoxin
6-deoxy-erythononlide B
cladinose
desosamine
isoprene unit
b) otherwise... shikimate