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The Acetate Pathway:

Fatty Acids and Polyketides


(ATP, 2016)

fatty acids
poly--keto
chains

prostaglan
dins
macrolide
antibiotics

Polyketide
s

aromatic
compound
s

Fatty Acids Synthase


(FAS):
Saturated Fatty Acids
FAS

Animal

Fungal

Large
multifunctional
protein with
seven discrete
functional
domains on a
single
polypeptide
encoded by a
single gene
(homodimer)

Multifunctional
enzyme with
seven discrete
functional
domains on two
non identical
polypeptides
and encoded
by a single gene
(66
dodecamer)

Bacteria &
Plant

An assembly
of separable
enzymes,
encoded by
seven
different
genes

Saturated Fatty Acids


Pathway

Enzyme Activities of
Mammalian FAS

FAS in
bacteria
and
plants

a series of discrete proteins


each of which catalyses an
individual reaction of the fatty
acid biosynthetic pathway

In some cases, two or more


enzymes are able to perform the
same chemical reaction, but
have differing substrate
specificities

For example:
three distinct KS
activities with
characteristic
chain-length
specificities have
been identified in
plants.
One condenses
acetyl-CoA with
malonyl-ACP,
one is responsible

Fatty Acids
Animal
Saturate
d Fatty
Acid

Solid

Plant &
Fish
Unsatura
ted Fatty
Acid

Liquid

Unsaturated Fatty Acids Pathway:


Desaturation of Alcanoic Acid

9-desaturase enzyme
introduced a cis double
bond into a saturated fatty
acid, requiring O2 and
NADPH or NADH cofactors

prostaglandins
modified
C20 fatty
acids

first
isolated
from
human
semen
and
initially
assumed
to be
secreted
by the
prostate
gland

regulate
blood
exert a
pressure,
occur
wide
contractio
widely in variety of
ns of
animal
pharmacol
smooth
tissues,
ogical
muscle,
but only in effects on
gastric
tiny
humans
secretion,
amounts
and
and
animals
platelet
aggregati
on

Polyketide Synthases
(PKSs)
Type I
Type II
large multifunctional proteins with individual
functional domains

Iterative

Non-iterative

use their functional


domains repeatedly
to produce a
particular polyketide

possess a distinct
active site for every
enzyme-catalysed
step

complex of individual
monofunctional
proteins

Iteractive

Macrolides
macrocyclic lactones with a ring size typically 1216
atoms, and with extensive branching through methyl
substituents.
Two or more sugar units are attached through glycoside
linkages; these sugars tend to be unusual 6-deoxy
structures often restricted to this class of compounds.
Examples include l-cladinose, l-mycarose, d-mycinose,
and l-oleandrose.
At least one sugar is an amino sugar, e.g. d-desosamine,
d-forosamine, and d-mycaminose.
These antibiotics have a narrow spectrum of
antibacterial activity, principally against Gram-positive
microorganisms.
Their antibacterial spectrum resembles, but is not
identical to, that of the penicillins, so they provide a
valuable alternative for patients allergic to the
penicillins.

Macrolide
Pathway

Saccharopolyspora
erythraea

Biosynthetic Origins of the Basic


Macrolide

Aromatics

THAN
K YOU

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