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Information on EC 2.3.1.85 - fatty-acid synthase system
for references in articles please use BRENDA:EC2.3.1.85
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EC Tree 2 Transferases
2.3 Acyltransferases
2.3.1 Transferring groups other than aminoacyl groups
2.3.1.85 fatty-acid synthase system
IUBMB Comments
The animal enzyme is a multi-functional protein catalysing the reactions of EC 2.3.1.38 [acyl-carrier-protein] S-acetyltransferase, EC 2.3.1.39 [acyl-carrier-protein] S-malonyltransferase, EC 2.3.1.41 β-ketoacyl-[acyl-carrier-protein] synthase I, EC 1.1.1.100 3-oxoacyl-[acyl-carrier-protein] reductase, EC 4.2.1.59 3-hydroxyacyl-[acyl-carrier-protein] dehydratase, EC 1.3.1.39 enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific) and EC 3.1.2.14 oleoyl-[acyl-carrier-protein] hydrolase. cf. EC 2.3.1.86, fatty-acyl-CoA synthase system.
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
- 2.3.1.85
- mycobacterium
- tuberculosis
-
mycolic
-
lipogenic
-
enoyl
-
fasciclin
- cerulenin
-
beta-ketoacyl-acyl
- malonyl-coa
- triclosan
- isoniazid
-
transacylase
-
enoyl-acyl
-
beta-ketoacyl
- thiolactomycin
- malonyl-acp
-
condensing
- acyl-acps
-
malonyl
- srebp-1c
-
fabgs
- medicine
- apicoplast
-
boutons
-
phosphopantetheinylation
- 4'-phosphopantetheine
-
ketoacyl
-
antituberculous
- thiacetazone
- nutrition
- analysis
Reaction Schemes
show+
7
+
14
+
14
=
+
8
+
7
+
14
+
6
Synonyms
fasii, fatty-acid synthase, fas-ii, type ii fatty acid synthase, yeast fatty acid synthase, fatty acid synthase ii, fatty acid synthase i, type 2 fatty acid synthase, fatty acid synthase type 2, f09e10.3 protein, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
FAS
FAS-II
FASII
FASN
fatty acid synthase
fatty acid synthase type 2
-
3-oxoacyl-acyl carrier protein reductase FabG1/Rv1483 is a component of the fatty acid synthase type 2 system
fatty-acid synthase
-
-
-
-
type 2 fatty acid synthase
type II fatty acid synthase
yeast fatty acid synthase
-
-
-
-
FAS
-
-
-
-
type 2 fatty acid synthase
-
3-oxoacyl-acyl carrier protein reductase is a component of the type 2 fatty acid synthase system
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
reaction mechanism
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
reaction mechanism
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
reaction mechanism
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
reaction mechanism
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
reaction mechanism
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
reaction mechanism
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
reaction mechanism
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
reaction mechanism
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
reaction mechanism
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
structure and regulation
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
structure and regulation
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
structure and regulation
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
structure and regulation
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
structure and regulation
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
structure and regulation
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
structure and regulation
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
structure and regulation
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
structure and regulation
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
structure and regulation
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
scheme of functional interactions between constituent domains. A single subunit, in context of a dimer, is able to catalyze the entire biosynthetic pathway
-
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acyl group transfer
-
-
-
-
decarboxylation
-
-
-
-
redox reaction
-
-
-
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thioester hydrolysis
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
MetaCyc
fatty acid biosynthesis initiation (type I), palmitate biosynthesis I (type I fatty acid synthase)
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SYSTEMATIC NAME
IUBMB Comments
acyl-CoA:malonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing and thioester-hydrolysing)
The animal enzyme is a multi-functional protein catalysing the reactions of EC 2.3.1.38 [acyl-carrier-protein] S-acetyltransferase, EC 2.3.1.39 [acyl-carrier-protein] S-malonyltransferase, EC 2.3.1.41 beta-ketoacyl-[acyl-carrier-protein] synthase I, EC 1.1.1.100 3-oxoacyl-[acyl-carrier-protein] reductase, EC 4.2.1.59 3-hydroxyacyl-[acyl-carrier-protein] dehydratase, EC 1.3.1.39 enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific) and EC 3.1.2.14 oleoyl-[acyl-carrier-protein] hydrolase. cf. EC 2.3.1.86, fatty-acyl-CoA synthase system.
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CAS REGISTRY NUMBER
COMMENTARY
9045-77-6
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3-hydroxybutanoyl-CoA + an [acyl-carrier protein]
CoA + 3-hydroxybutanoyl-[acyl-carrier protein]
Substrates: -
Products: -
Products: -
?
3-methylbutanoyl-CoA + an [acyl-carrier protein]
CoA + 3-methylbutanoyl-[acyl-carrier protein]
Substrates: -
Products: -
Products: -
?
acetoacetyl-CoA + an [acyl-carrier protein]
CoA + acetoacetyl-[acyl-carrier protein]
Substrates: -
Products: -
Products: -
?
acetoacetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+
a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
Substrates: -
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
acetyl-CoA + an [acyl-carrier protein]
CoA + acetyl-[acyl-carrier protein]
Substrates: -
Products: -
Products: -
?
acetyl-CoA + malonyl-CoA + NADH
palmitate + CoA + CO2 + NAD+
-
Substrates: -
Products: -
Products: -
?
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+
a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
Substrates: -
Products: -
Products: -
?
butanoyl-CoA + an [acyl-carrier protein]
CoA + butanoyl-[acyl-carrier protein]
Substrates: -
Products: -
Products: -
?
butanoyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+
a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
Substrates: -
Products: -
Products: -
?
crotonyl-CoA + an [acyl-carrier protein]
CoA + crotonyl-[acyl-carrier protein]
Substrates: -
Products: -
Products: -
?
malonyl-CoA + an [acyl-carrier protein]
CoA + a malonyl-[acyl-carrier protein]
Substrates: -
Products: -
Products: -
?
methylmalonyl-CoA + an [acyl-carrier protein]
CoA + a methylmalonyl-[acyl-carrier protein]
Substrates: -
Products: -
Products: -
?
octanoyl-CoA + an [acyl-carrier protein]
CoA + octanoyl-[acyl-carrier protein]
Substrates: -
Products: -
Products: -
?
octanoyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+
a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
Substrates: -
Products: -
Products: -
?
palmitoyl-CoA + an [acyl-carrier protein]
CoA + palmitoyl-[acyl-carrier protein]
Substrates: -
Products: -
Products: -
?
phenylacetyl-CoA + an [acyl-carrier protein]
CoA + phenylacetyl-[acyl-carrier protein]
Substrates: -
Products: -
Products: -
?
succinyl-CoA + an [acyl-carrier protein]
CoA + succinyl-[acyl-carrier protein]
Substrates: -
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: C20 and C22 fatty acids in the absence of thioesterase activity
Products: C20 and C22 fatty acids in the absence of thioesterase activity
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: methylmalonyl-CoA instead of malonyl-CoA yields branched fatty acid, e.g. 2,4,6,8-tetramethyldecanoic acid
Products: methylmalonyl-CoA instead of malonyl-CoA yields branched fatty acid, e.g. 2,4,6,8-tetramethyldecanoic acid
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: C20 and C22 fatty acids in the absence of thioesterase activity
Products: C20 and C22 fatty acids in the absence of thioesterase activity
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
Substrates: -
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: C20 and C22 fatty acids in the absence of thioesterase activity
Products: C20 and C22 fatty acids in the absence of thioesterase activity
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: decanoyl-CoA, acetyl-CoA, butyryl-CoA and malonyl-CoA are bound to the same active site
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: C20 and C22 fatty acids in the absence of thioesterase activity
Products: C20 and C22 fatty acids in the absence of thioesterase activity
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: specific for malonyl-CoA, acetyl-CoA can be replaced by propionyl-CoA or butyryl-CoA
Products: in the absence of NADPH the product is triacetic acid lactone
Products: in the absence of NADPH the product is triacetic acid lactone
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: FAS-A mainly synthesizes the C18 fatty acids oleate and stearate with only traces of palmitate, the major product of FAS-B is pamitate
Products: FAS-A mainly synthesizes the C18 fatty acids oleate and stearate with only traces of palmitate, the major product of FAS-B is pamitate
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: C20 and C22 fatty acids in the absence of thioesterase activity
Products: C20 and C22 fatty acids in the absence of thioesterase activity
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: in the absence of NADPH the product is triacetic acid lactone
Products: in the absence of NADPH the product is triacetic acid lactone
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: participates in energy metabolism in vivo which is related to adiposis and cancer
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: C20 and C22 fatty acids in the absence of thioesterase activity
Products: C20 and C22 fatty acids in the absence of thioesterase activity
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: acetoacetyl-CoA can substitute for acetyl-CoA
Products: small amounts of stearate and myristate are also produced
Products: small amounts of stearate and myristate are also produced
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
Substrates: -
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: C20 and C22 fatty acids in the absence of thioesterase activity
Products: C20 and C22 fatty acids in the absence of thioesterase activity
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: lactating mammary gland thioesterase II of fatty acid synthetase: products are medium chain fatty acids from C8 to C12
Products: lactating mammary gland thioesterase II of fatty acid synthetase: products are medium chain fatty acids from C8 to C12
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: C20 and C22 fatty acids in the absence of thioesterase activity
Products: C20 and C22 fatty acids in the absence of thioesterase activity
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: lactating mammary gland thioesterase II of fatty acid synthetase: products are medium chain fatty acids from C8 to C12
Products: lactating mammary gland thioesterase II of fatty acid synthetase: products are medium chain fatty acids from C8 to C12
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: C20 and C22 fatty acids in the absence of thioesterase activity
Products: C20 and C22 fatty acids in the absence of thioesterase activity
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: products are fatty acid chains from C14 to C20
Products: products are fatty acid chains from C14 to C20
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: in the absence of NADPH the product is triacetic acid lactone
Products: in the absence of NADPH the product is triacetic acid lactone
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: carries acetyl- and malonyl-CoA transacylase, condensing enzyme, beta-ketoacyl reductase, beta-hydroxyacyl dehydrase, enoylacyl reductase, palmitoyl-CoA thioesterase activities on each multifunctional subunit
Products: -
Products: -
?
additional information
?
-
-
Substrates: fatty acid synthetases of vertebrates and yeast are stable enzyme complexes of multifunctional polypeptide chains, the fatty acid synthetases of plants and E. coli consist of non-associated individual enzymes
Products: -
Products: -
?
additional information
?
-
-
Substrates: fatty acid synthase-dependent palmitoylation of epidermal growth factor receptor is required for epidermal growth factor receptor dimerization and kinase activation. Inhibition of fatty acid synthase or palmitoyl acyltransferases reduces the activity and down-regulated the levels of epidermal growth factor receptor, and sensitizes cancer cells to epidermal growth factor receptor tyrosine kinase inhibitors
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme generated signals are needed to support preadipocyte differentiation
Products: -
Products: -
?
additional information
?
-
Substrates: under non-reducing conditions in the absence of NADPH, FASN produces triacetic acid lactone with an averaged malonyl consumption rate of 46 nmol per min per mg protein
Products: -
Products: -
?
additional information
?
-
-
Substrates: fatty acid synthetases of vertebrates and yeast are stable enzyme complexes of multifunctional polypeptide chains, the fatty acid synthetases of plants and E. coli consist of non-associated individual enzymes
Products: -
Products: -
?
additional information
?
-
-
Substrates: synthesizes equal amounts of C14 and C16 fatty acids
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
additional information
?
-
-
Substrates: enzyme generated signals are needed to support preadipocyte differentiation
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: participates in energy metabolism in vivo which is related to adiposis and cancer
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
-
Substrates: multifunctional enzyme, involved in animal fat synthesis
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4'-phosphopantetheine
-
requirement, 1 mol associated with 1 mol subunit
4'-phosphopantetheine
-
requirement, 1 mol associated with 1 mol subunit
4'-phosphopantetheine
-
requirement, 1 mol associated with 1 mol subunit
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(+)-catechin
-
50% inhibition of overall enzyme reaction at 1.6 mM, 50% inhibition of ketoacyl reduction reaction at 7.4 mM
(-)-catechin gallate
-
50% inhibition at 0.0015 mg/ml, B ring, C ring and gallate ring of inhibitor react with acyl transferase domain
(-)-epicatechin
-
50% inhibition of overall enzyme reaction at 3.8 mM, 50% inhibition of ketoacyl reduction reaction at 9.38 mM
(-)-epicatechin gallate
-
50% inhibition of overall enzyme reaction at 0.042 mM, 50% inhibition of ketoacyl reduction reaction at 0.068 mM, two-step inhibition mechanism with reversible initial inhibition and irreversible subsequent inactivation
(-)-epigallocatechin gallate
-
0.5 mM, 20% residual activity, 50% inhibition of overall enzyme reaction at 0.052 mM, 50% inhibition of ketoacyl reduction reaction at 0.1 mM
(10E,12Z)-octadec-10,12-dienoic acid
-
more potent inhibitor than (9Z,11E)-octadec-9,11-dienoic acid
(2-(5-chloro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-yl) (4-(1-hydroxy cyclo propane-1-carbonyl) piperazin-1-yl)methanone
treatment leads to cell cycle arrest in Sub-G1/S phase along with induction of apoptosis
-
(2-(5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-yl)(4-(1-hydroxy cyclo propane-1-carbonyl)piperazin-1-yl)methanone
-
-
(4-(cyclopropanecarbonyl)piperazin-1-yl)(2-(5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-yl)methanone
-
-
1,1'-[methanediylbis(2,4,6-trihydroxy-5-methylbenzene-3,1-diyl)]dibutan-1-one
-
IC50: 0.0254 mM
1,2,3,4,6-penta-O-galloyl-beta-D-glucose
-
compound is transported across cancer cell membrane to further down-regulate FAS and activate caspase-3 in MDA-MB-231 cells. Compared with other FAS inhibitors, including catechin gallate and morin, 1,2,3,4,6-penta-O-galloyl-beta-D-glucose involves a higher reversible fast-binding inhibition with an irreversible slow-binding inhibition, i.e. saturation kinetics with a dissociation constant of 0.59 microM and a limiting rate constant of 0.16 per min. The major reacting site of PGG is on the beta-ketoacyl reduction domain of FAS. Compound exhibits different types of inhibitions against the three substrates in the FAS overall reaction
2,2'-methanediylbis(3,5-dihydroxy-4,4-dimethyl-6-propanoylcyclohexa-2,5-dien-1-one)
-
IC50: 0.0602 mM
2,3-trans-octenoyl-CoA
-
competitively inhibits malonyl-transferase reaction
2-(3-butanoyl-2,4,6-trihydroxy-5-methylbenzyl)-3,5-dihydroxy-4,4-dimethyl-6-propanoylcyclohexa-2,5-dien-1-one
-
IC50: 0.0231 mM
2-acetyl-6-(3-butanoyl-2,4,6-trihydroxy-5-methylbenzyl)-3,5-dihydroxy-4,4-dimethylcyclohexa-2,5-dien-1-one
-
IC50: 0.0287 mM
2-acetyl-6-(3-butanoyl-2,4,6-trihydroxybenzyl)-3,5-dihydroxy-4,4-dimethylcyclohexa-2,5-dien-1-one
-
IC50: 0.0297 mM
2-acetyl-6-[(2,4-dihydroxy-3,3-dimethyl-6-oxo-5-propanoylcyclohexa-1,4-dien-1-yl)methyl]-3,5-dihydroxy-4,4-dimethylcyclohexa-2,5-dien-1-one
-
IC50: 0.0717 mM
2-acetyl-6-{3-butanoyl-5-[(2,4-dihydroxy-3,3-dimethyl-6-oxo-5-propanoylcyclohexa-1,4-dien-1-yl)methyl]-2,4,6-trihydroxybenzyl}-3,5-dihydroxy-4,4-dimethylcyclohexa-2,5-dien-1-one
-
IC50: 0.031 mM
2-butanoyl-6-(3-butanoyl-2,6-dihydroxy-4-methoxy-5-methylbenzyl)-3,5-dihydroxy-4,4-dimethylcyclohexa-2,5-dien-1-one
-
IC50: 0.0326 mM
2-butanoyl-6-[(2,4-dihydroxy-3,3-dimethyl-6-oxo-5-propanoylcyclohexa-1,4-dien-1-yl)methyl]-3,5-dihydroxy-4,4-dimethylcyclohexa-2,5-dien-1-one
-
IC50: 0.0561 mM
2-[(Z)-[2-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]hydrazinylidene]methyl]pyridine
good inhibition activity against two enzyme overexpressing cancer cell lines. IC50 value for MDA-MB-468 cell 0.0083 mM, for SW-480 cell 0.0015 mM
3,4-dihydroxybenzoic acid
-
50% inhibition of overall enzyme reaction at 9.0 mM, 50% inhibition of ketoacyl reduction reaction at 30 mM
3-hydroxynaphthalen-1-yl 3,4,5-trihydroxybenzoate
analog of (-)-epigallocatechin 3-gallate. Compound displays moderate to high cytotoxicity and significantly blocks FASN activity, diminishes FASN protein expression levels and induces apoptosis
4-hydroxynaphthalen-2-yl 3,4,5-trihydroxybenzoate
analog of (-)-epigallocatechin 3-gallate. Compound displays moderate to high cytotoxicity and significantly blocks FASN activity, diminishes FASN protein expression levels and induces apoptosis
adriamycin
-
cytotoxic activity against cancer cells, IC50 value for MCF-7 cell 0.0035 mM, for A-549 cell 0.0018 mM, for HL-60 cell 0.0008 mM
catechin gallate
-
very potent inhibitor, acts mainly on an acyl transferase domain. IC50 of 0.0015 mg/ml
catechol
-
50% inhibition of overall enzyme reaction at 7.4 mM, 50% inhibition of ketoacyl reduction reaction at 21 mM
dutasteride
-
at clinically relevant levels, inhibits FASN mRNA, protein expression and enzymatic activity in prostate cancer cells
ethyl 4-(2-(5-chloro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carbonyl) piperazine-1-carboxylate
treatment leads to cell cycle arrest in Sub-G1/S phase along with induction of apoptosis
-
ethyl 4-(2-(5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carbonyl) piperazine-1-carboxylate
-
-
gallic acid
-
50% inhibition of overall enzyme reaction at 21 mM, 50% inhibition of ketoacyl reduction reaction at 26 mM
grape skin extract
-
inhibits the overall reaction and beta-ketoacyl reductase reaction of FAS with IC50 values of 4.61 microg/ml and 20.3 microg/ml, respectively. Inhibits the overall reaction of FAS competitively with acetyl-CoA, noncompetitively with malonyl-CoA and in a mixed manner with NADPH
-
N-ethylmaleimide
-
inhibition of elongation process and malonyl transfer at 10 mM
naphthalene-1,3-diyl bis(3,4,5-trihydroxybenzoate)
analog of (-)-epigallocatechin 3-gallate. Compound displays moderate to high cytotoxicity and significantly blocks FASN activity, diminishes FASN protein expression levels
nordihydroguaiaretic acid
-
inhibits competitively with respect to acetyl-CoA, noncompetitively with respect to malonyl-CoA, and in a mixed manner with respect toNADPH.IC50 = 0.093 mM
procyanidin
-
procyanidins isolated from seeds of Hippophae rhamnoides inhibits the activity of FAS and reduces MDA-MB-231 cell viability with an IC50 value of 37.5 microg/ml. Procyanidins induce MDA-MB-231 cell apoptosis
propyl gallate
-
50% inhibition of overall enzyme reaction at 0.5 mM, 50% inhibition of ketoacyl reduction reaction at 1.4 mM
propyl p-hydroxylbenzoate
-
50% inhibition of overall enzyme reaction at 1.1 mM, 50% inhibition of ketoacyl reduction reaction at 2.6 mM
Zn2+
-
80% loss of activity at 0.008 mM, interacts with SH groups, substrates of the reaction protect, malonyl-CoA being the most effective, addition of dithiothreitol leads to a recovery of 70% enzyme activity; below 0.004 mM, rapid and irreversible inactivation, above 0.004 mM, cross-linking of enzyme involving phosphopantheine SH group. All three substrates, acetyl-CoA, malonyl-CoA, NADPH, protect. Renaturation by dithiothreitol
[1,1'-biphenyl]-4,4'-diyl bis(3,4,5-trihydroxybenzoate)
analog of (-)-epigallocatechin 3-gallate. Compound displays moderate to high cytotoxicity and significantly blocks FASN activity
1,3-Dibromo-2-propanone
-
acetyl-CoA, not malonyl-CoA, protects against inactivation, both protect against cross-linking of the subunits; covalently cross-links subunits, inactivates beta-ketoacyl synthetase- and overall-fatty acid synthase reaction
1,3-Dibromo-2-propanone
-
acetyl-CoA, not malonyl-CoA, protects against inactivation, both protect against cross-linking of the subunits
C75
-
0.05 mM, 90% reduction of enzyme activity, dramatic reduction of visible lipid droplet accumulation, reduction of enzyme mRNA
C75
-
inactivation of beta-ketoacyl synthase, enoyl reductase and thioesterase partial activites, mechanism
C75
-
i.e. 3-carboxy-4-octyl-2-methylenebutyrolactone, 50% inhibition of enzyme at 0.2 mM
cerulenin
-
0.01 mM, 75% reduction of enzyme activity, dramatic reduction of visible lipid droplet accumulation, reduction of enzyme mRNA
ginkgolic acid C15:1
-
DELTA8 and DELTA10 isomers, at ratio 1:2. Cytotoxic activity against cancer cells, IC50 value for MCF-7 cell 0.146 mM, for A-549 cell 0.066 mM, for HL-60 cell 0.005 mM
ginkgolic acid C17:1
-
double bond positions not specified. Cytotoxic activity against cancer cells, IC50 value for MCF-7 cell 0.093 mM, for A-549 cell 0.050 mM, for HL-60 cell 0.004 mM
ginkgolic acid C17:2
-
double bond positions not specified. Cytotoxic activity against cancer cells, IC50 value for MCF-7 cell 0.108 mM, for A-549 cell 0.056 mM, for HL-60 cell 0.004 mM
iodoacetamide
-
beta-ketoacyl synthetase activity, acetyl-CoA but not malonyl-CoA protects
iodoacetamide
-
beta-ketoacyl synthetase activity, acetyl-CoA but not malonyl-CoA protects
iodoacetamide
-
beta-ketoacyl synthetase activity, acetyl-CoA but not malonyl-CoA protects
iodoacetamide
-
kinetics, 50% inactivation after 5 min at 1 mM and after 0.5 min at 20 mM
iodoacetamide
-
beta-ketoacyl synthetase activity, acetyl-CoA but not malonyl-CoA protects
iodoacetamide
-
beta-ketoacyl synthetase activity, acetyl-CoA but not malonyl-CoA protects
iodoacetamide
-
inhibits beta-ketoacyl synthetase activity, acetyl-CoA but not malonyl CoA protects
iodoacetamide
-
beta-ketoacyl synthetase activity, acetyl-CoA but not malonyl-CoA protects
iodoacetamide
-
beta-ketoacyl synthetase activity, acetyl-CoA but not malonyl-CoA protects
iodoacetamide
-
beta-ketoacyl synthetase activity, acetyl-CoA but not malonyl-CoA protects
iodoacetamide
-
beta-ketoacyl synthetase activity, acetyl-CoA but not malonyl-CoA protects
quercetin
-
50% inhibition at 0.0024 mg/ml, mixed type inhibition for substrate NADPH, competitive with substrate acetyl-CoA, noncompetitive with malonyl-CoA
resveratrol
-
inhibits the overall reaction and beta-ketoacyl reductase reaction of FAS with IC50 values of 11.1 microg/ml and 21.9 microg/ml, respectively. In 3 T3-L1 preadipocytes, resveratrol reduces lipid accumulation remarkably
S-(4-bromo-2,3-dioxobutyl)-CoA
-
irreversible, acetyl transacetylase and beta-ketoacyl synthase activity, 4 mol inhibitor per mol enzyme complex, mechanism, dithiothreitol protects
S-(4-bromo-2,3-dioxobutyl)-CoA
-
irreversible, 50% inhibition after 10 s at 0.02 mM, 6.5 s at 0.06 mM and 4.5 s at 0.09 mM, specific for acetyl transacetylase and beta-ketoacyl synthase activity, 4 mol inhibitor per mol enzyme complex, acetyl-CoA, malonyl-CoA, cysteine and pantetheine protect
triclosan
-
0.05 mM, 70% reduction of enzyme activity, dramatic reduction of visible lipid droplet accumulation, reduction of enzyme mRNA
triclosan
-
inititation of mammary carcinogenesis is reduced in animals fed with triclosan, triclosan also inhibits enzyme activity in tumor cell homogenates
Urea
-
enzyme forms inactive aggregates in the presence of urea, cyclodextrins prevent aggregation
Urea
-
non-competitive inhibitor for NADPH, competitive inhibitor for acetyl-CoA and malonyl-CoA, complete inactivation occurs at lower concentration than obvious conformational changes, aggregation occurs at 3-4 M
additional information
-
the enzyme is potently inhibited by green tea extract
-
additional information
-
a common model is proposed that is possibly shared by all FAS polyphenol inhibitors. The model includes two almost planar aromatic rings with their respective hydroxyl groups, and a proper ester linkage between the two rings that possibly causes the inhibition of FAS by irreversibly inhibiting the beta-ketoacyl reductase domain
-
additional information
-
FAS is potently inhibited by extracts of Taxillus chinensis Danser. Potent, reversible and a fast irreversible inhibition. IC50: 480 ng/ml
-
additional information
-
inhibition by extract from rhizome of Alpinia officinarum, i.e. galangal. Inhibition consists of both reversible inhibition with an IC50-value of 0.0017 mg dried extract per ml, and biphasic slow-binding inactivation
-
additional information
-
black tea extract shows more potent inhibitory activity on fatty acid synthase than green tea extract. Inhibitory ability of the black tea extract depends on the extracting solvent and the conditions used. Only 1023% of the inhibitory activity from the black tea is extracted by the general method of boiling with water. The results suggest that the main fatty acid synthase inhibitors in black tea might be theaflavins
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Atherosclerosis
Macrophage fatty-acid synthase deficiency decreases diet-induced atherosclerosis.
Breast Neoplasms
Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts.
Chronic Periodontitis
Structural characterization of Porphyromonas gingivalis enoyl-ACP reductase II (FabK).
Dehydration
Covalent modification of the Mycobacterium tuberculosis FAS-II dehydratase by Isoxyl and Thiacetazone.
Dehydration
Mechanisms of Resistance Associated with the Inhibition of the Dehydration Step of Type II Fatty Acid Synthase in Mycobacterium tuberculosis.
Dehydration
The missing piece of the type II fatty acid synthase system from Mycobacterium tuberculosis.
fatty-acid synthase system deficiency
Macrophage fatty-acid synthase deficiency decreases diet-induced atherosclerosis.
Infections
Permissive Fatty Acid Incorporation Promotes Staphylococcal Adaptation to FASII Antibiotics in Host Environments.
Infections
Structural and biological evaluation of a novel series of benzimidazole inhibitors of Francisella tularensis enoyl-ACP reductase (FabI).
Insulin Resistance
Antiobesity efficacy of asiatic acid: down-regulation of adipogenic and inflammatory processes in high fat diet induced obese rats.
Insulin Resistance
ChREBP binding and histone modifications modulate hepatic expression of the Fasn gene in a metabolic syndrome rat model.
Insulin Resistance
Effects of extended-release niacin on lipid profile and adipocyte biology in patients with impaired glucose tolerance.
Malaria
2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections.
Malaria
2-Octadecynoic acid as a dual life stage inhibitor of Plasmodium infections and plasmodial FAS-II enzymes.
Malaria
Characterization of the Plasmodium falciparum and P. berghei glycerol 3-phosphate acyltransferase involved in FASII fatty acid utilization in the malaria parasite apicoplast.
Malaria
Expression, purification and crystallization of the Plasmodium falciparum enoyl reductase.
Malaria
Type II fatty acid biosynthesis is essential for Plasmodium falciparum sporozoite development in the midgut of Anopheles mosquitoes.
Neoplasms
4-methylene-2-octyl-5-oxotetrahydrofuran-3-carboxylic acid (C75), an inhibitor of fatty-acid synthase, suppresses the mitochondrial fatty acid synthesis pathway and impairs mitochondrial function.
Neoplasms
Antiobesity efficacy of asiatic acid: down-regulation of adipogenic and inflammatory processes in high fat diet induced obese rats.
Neoplasms
Characterization and inhibition of fatty acid synthase in pediatric tumor cell lines.
Neoplasms
Fatty acid synthase as a tumor marker: its extracellular expression in human breast cancer.
Neoplasms
Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology.
Neoplasms
Inhibition of fatty-acid synthase induces caspase-8-mediated tumor cell apoptosis by up-regulating DDIT4.
Neoplasms
Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts.
Neoplasms
Proto-oncogene FBI-1 (Pokemon) and SREBP-1 Synergistically Activate Transcription of Fatty-acid Synthase Gene (FASN).
Neoplasms
The galloyl moiety of green tea catechins is the critical structural feature to inhibit fatty-acid synthase.
Neuroblastoma
Characterization and inhibition of fatty acid synthase in pediatric tumor cell lines.
Obesity
Identification and structural characterization of an unusual mycobacterial monomeromycolyl-diacylglycerol.
Polycystic Kidney Diseases
A C. elegans model for mitochondrial fatty acid synthase II: the longevity-associated gene W09H1.5/mecr-1 encodes a 2-trans-enoyl-thioester reductase.
Prostatic Neoplasms
Association of fatty-acid synthase polymorphisms and expression with outcomes after radical prostatectomy.
Retinoblastoma
Characterization and inhibition of fatty acid synthase in pediatric tumor cell lines.
Rhabdoid Tumor
Characterization and inhibition of fatty acid synthase in pediatric tumor cell lines.
Sepsis
Permissive Fatty Acid Incorporation Promotes Staphylococcal Adaptation to FASII Antibiotics in Host Environments.
Toxoplasmosis
Apicoplast-Localized Lysophosphatidic Acid Precursor Assembly Is Required for Bulk Phospholipid Synthesis in Toxoplasma gondii and Relies on an Algal/Plant-Like Glycerol 3-Phosphate Acyltransferase.
Tuberculosis
A common mechanism of inhibition of the Mycobacterium tuberculosis mycolic acid biosynthetic pathway by isoxyl and thiacetazone.
Tuberculosis
A novel interaction linking the FAS-II and phthiocerol dimycocerosate (PDIM) biosynthetic pathways.
Tuberculosis
AccD6, a key carboxyltransferase essential for mycolic acid synthesis in Mycobacterium tuberculosis, is dispensable in a nonpathogenic strain.
Tuberculosis
AccD6, a member of the Fas II locus, is a functional carboxyltransferase subunit of the acyl-coenzyme A carboxylase in Mycobacterium tuberculosis.
Tuberculosis
AcpM, the meromycolate extension acyl carrier protein of Mycobacterium tuberculosis, is activated by the 4'-phosphopantetheinyl transferase PptT, a potential target of the multistep mycolic acid biosynthesis.
Tuberculosis
Analogs of the antituberculous agent pyrazinamide are competitive inhibitors of NADPH binding to M. tuberculosis fatty acid synthase I.
Tuberculosis
Biochemical characterization of acyl carrier protein (AcpM) and malonyl-CoA:AcpM transacylase (mtFabD), two major components of Mycobacterium tuberculosis fatty acid synthase II.
Tuberculosis
Characterization and site-directed mutagenesis of the putative novel acyl carrier protein Rv0033 and Rv1344 from Mycobacterium tuberculosis.
Tuberculosis
Characterization of Mycobacterium smegmatis expressing the Mycobacterium tuberculosis fatty acid synthase I (fas1) gene.
Tuberculosis
Covalent modification of the Mycobacterium tuberculosis FAS-II dehydratase by Isoxyl and Thiacetazone.
Tuberculosis
Crystal structure of MabA from Mycobacterium tuberculosis, a reductase involved in long-chain fatty acid biosynthesis.
Tuberculosis
Crystal structure of the Mycobacterium tuberculosis enoyl-ACP reductase, InhA, in complex with NAD+ and a C16 fatty acyl substrate.
Tuberculosis
Detection and Confirmation of Alkaloids in Leaves of Justicia adhatoda and Bioinformatics Approach to Elicit Its Anti-tuberculosis Activity.
Tuberculosis
Development of a scintillation proximity assay for the Mycobacterium tuberculosis KasA and KasB enzymes involved in mycolic acid biosynthesis.
Tuberculosis
Expression of a recombinant, 4'-Phosphopantetheinylated, active M. tuberculosis fatty acid synthase I in E. coli.
Tuberculosis
Expression, purification, and characterization of the Mycobacterium tuberculosis acyl carrier protein, AcpM.
Tuberculosis
Flavonoid inhibitors as novel antimycobacterial agents targeting Rv0636, a putative dehydratase enzyme involved in Mycobacterium tuberculosis fatty acid synthase II.
Tuberculosis
Function of heterologous Mycobacterium tuberculosis InhA, a type 2 fatty acid synthase enzyme involved in extending C20 fatty acids to C60-to-C90 mycolic acids, during de novo lipoic acid synthesis in Saccharomyces cerevisiae.
Tuberculosis
Inhibition of isolated Mycobacterium tuberculosis fatty acid synthase I by pyrazinamide analogs.
Tuberculosis
Inhibitory activity of pentacyano(isoniazid)ferrate(II), IQG-607, against promastigotes and amastigotes forms of Leishmania braziliensis.
Tuberculosis
Lack of Specificity of Phenotypic Screens for Inhibitors of the Mycobacterium tuberculosis FAS-II System.
Tuberculosis
Ligand-induced fit in mycobacterial MabA: the sequence-specific C-terminus locks the conformational change.
Tuberculosis
MabA (FabG1), a Mycobacterium tuberculosis protein involved in the long-chain fatty acid elongation system FAS-II.
Tuberculosis
Mechanisms of Resistance Associated with the Inhibition of the Dehydration Step of Type II Fatty Acid Synthase in Mycobacterium tuberculosis.
Tuberculosis
Physiological Function of Mycobacterial mtFabD, an Essential Malonyl-CoA:AcpM Transacylase of Type 2 Fatty Acid Synthase FASII, in Yeast mct1Delta Cells.
Tuberculosis
Point mutations within the fatty acid synthase type II dehydratase components HadA or HadC contribute to isoxyl resistance in Mycobacterium tuberculosis.
Tuberculosis
Probing reactivity and substrate specificity of both subunits of the dimeric Mycobacterium tuberculosis FabH using alkyl-CoA disulfide inhibitors and acyl-CoA substrates.
Tuberculosis
Purification and biochemical characterization of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthases KasA and KasB.
Tuberculosis
Pyrazinamide, but not pyrazinoic acid, is a competitive inhibitor of NADPH binding to Mycobacterium tuberculosis fatty acid synthase I.
Tuberculosis
Rv3080c regulates the rate of inhibition of mycobacteria by isoniazid through FabD.
Tuberculosis
The condensing activities of the Mycobacterium tuberculosis type II fatty acid synthase are differentially regulated by phosphorylation.
Tuberculosis
The missing piece of the type II fatty acid synthase system from Mycobacterium tuberculosis.
Tuberculosis
The Mycobacterium tuberculosis FAS-II condensing enzymes: their role in mycolic acid biosynthesis, acid-fastness, pathogenesis and in future drug development.
Tuberculosis
The Mycobacterium tuberculosis FAS-II dehydratases and methyltransferases define the specificity of the mycolic acid elongation complexes.
Tuberculosis
The new tuberculosis drug Perchlozone(®) shows cross-resistance with thiacetazone.
Tuberculosis
Triclosan inhibition of mycobacterial InhA in Saccharomyces cerevisiae: yeast mitochondria as a novel platform for in vivo antimycolate assays.
Tuberculosis
X-ray crystal structure of Mycobacterium tuberculosis beta-ketoacyl acyl carrier protein synthase II (mtKasB).
Urinary Bladder Neoplasms
Inhibition of Fatty-acid Synthase Suppresses P-AKT and Induces Apoptosis in Bladder Cancer.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00172
3-hydroxybutanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.00206
3-methylbutanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.00086
acetoacetyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.00164
butanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.00136
crotonyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.00062
methylmalonyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.00073
octanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.0048
palmitoyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.00096
phenylacetyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.0021
succinyl-CoA
didomain construct, pH not specified in the publication, 25°C
additional information
additional information
-
Km-values for various partial activities of fatty acid synthetase
-
0.00163
acetyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.003
acetyl-CoA
didomain construct bearing mutation R606A, pH not specified in the publication, 25°C
0.00128
malonyl-CoA
didomain construct, pH not specified in the publication, 25°C
0.018
malonyl-CoA
didomain construct bearing mutation R606A, pH not specified in the publication, 25°C
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
6.1
3-hydroxybutanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
7.2
3-methylbutanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
7.3
acetoacetyl-CoA
didomain construct, pH not specified in the publication, 25°C
10.8
butanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
6
crotonyl-CoA
didomain construct, pH not specified in the publication, 25°C
4
methylmalonyl-CoA
didomain construct, pH not specified in the publication, 25°C
4.1
octanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
2.5
palmitoyl-CoA
didomain construct, pH not specified in the publication, 25°C
6
phenylacetyl-CoA
didomain construct, pH not specified in the publication, 25°C
13.4
succinyl-CoA
didomain construct, pH not specified in the publication, 25°C
13
acetyl-CoA
didomain construct bearing mutation R606A, pH not specified in the publication, 25°C
13.7
acetyl-CoA
didomain construct, pH not specified in the publication, 25°C
5
malonyl-CoA
didomain construct bearing mutation R606A, pH not specified in the publication, 25°C
15.6
malonyl-CoA
didomain construct, pH not specified in the publication, 25°C
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
8500
acetoacetyl-CoA
didomain construct, pH not specified in the publication, 25°C
6600
butanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
4400
crotonyl-CoA
didomain construct, pH not specified in the publication, 25°C
6500
methylmalonyl-CoA
didomain construct, pH not specified in the publication, 25°C
5600
octanoyl-CoA
didomain construct, pH not specified in the publication, 25°C
500
palmitoyl-CoA
didomain construct, pH not specified in the publication, 25°C
6200
phenylacetyl-CoA
didomain construct, pH not specified in the publication, 25°C
6400
succinyl-CoA
didomain construct, pH not specified in the publication, 25°C
4000
acetyl-CoA
didomain construct bearing mutation R606A, pH not specified in the publication, 25°C
8400
acetyl-CoA
didomain construct, pH not specified in the publication, 25°C
300
malonyl-CoA
didomain construct bearing mutation R606A, pH not specified in the publication, 25°C
12200
malonyl-CoA
didomain construct, pH not specified in the publication, 25°C
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0025
(2-(5-chloro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-yl) (4-(1-hydroxy cyclo propane-1-carbonyl) piperazin-1-yl)methanone, (2-(5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-yl)(4-(1-hydroxy cyclo propane-1-carbonyl)piperazin-1-yl)methanone, (4-(cyclopropanecarbonyl)piperazin-1-yl)(2-(5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-yl)methanone
Homo sapiens
pH not specified in the publication, 37°C
-
0.0254
1,1'-[methanediylbis(2,4,6-trihydroxy-5-methylbenzene-3,1-diyl)]dibutan-1-one
Gallus gallus
-
IC50: 0.0254 mM
0.0016
1,2,3,4,6-penta-O-galloyl-beta-D-glucose
Homo sapiens
-
37°C, pH not specified in the publication
0.0602
2,2'-methanediylbis(3,5-dihydroxy-4,4-dimethyl-6-propanoylcyclohexa-2,5-dien-1-one)
Gallus gallus
-
IC50: 0.0602 mM
0.0231
2-(3-butanoyl-2,4,6-trihydroxy-5-methylbenzyl)-3,5-dihydroxy-4,4-dimethyl-6-propanoylcyclohexa-2,5-dien-1-one
Gallus gallus
-
IC50: 0.0231 mM
0.0287
2-acetyl-6-(3-butanoyl-2,4,6-trihydroxy-5-methylbenzyl)-3,5-dihydroxy-4,4-dimethylcyclohexa-2,5-dien-1-one
Gallus gallus
-
IC50: 0.0287 mM
0.0297
2-acetyl-6-(3-butanoyl-2,4,6-trihydroxybenzyl)-3,5-dihydroxy-4,4-dimethylcyclohexa-2,5-dien-1-one
Gallus gallus
-
IC50: 0.0297 mM
0.0717
2-acetyl-6-[(2,4-dihydroxy-3,3-dimethyl-6-oxo-5-propanoylcyclohexa-1,4-dien-1-yl)methyl]-3,5-dihydroxy-4,4-dimethylcyclohexa-2,5-dien-1-one
Gallus gallus
-
IC50: 0.0717 mM
0.031
2-acetyl-6-{3-butanoyl-5-[(2,4-dihydroxy-3,3-dimethyl-6-oxo-5-propanoylcyclohexa-1,4-dien-1-yl)methyl]-2,4,6-trihydroxybenzyl}-3,5-dihydroxy-4,4-dimethylcyclohexa-2,5-dien-1-one
Gallus gallus
-
IC50: 0.031 mM
0.0326
2-butanoyl-6-(3-butanoyl-2,6-dihydroxy-4-methoxy-5-methylbenzyl)-3,5-dihydroxy-4,4-dimethylcyclohexa-2,5-dien-1-one
Gallus gallus
-
IC50: 0.0326 mM
0.0561
2-butanoyl-6-[(2,4-dihydroxy-3,3-dimethyl-6-oxo-5-propanoylcyclohexa-1,4-dien-1-yl)methyl]-3,5-dihydroxy-4,4-dimethylcyclohexa-2,5-dien-1-one
Gallus gallus
-
IC50: 0.0561 mM
0.0127
2-[(Z)-[2-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]hydrazinylidene]methyl]pyridine
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.003
ethyl 4-(2-(5-chloro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carbonyl) piperazine-1-carboxylate, ethyl 4-(2-(5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carbonyl) piperazine-1-carboxylate
Homo sapiens
pH not specified in the publication, 37°C
-
0.093
nordihydroguaiaretic acid
Anas platyrhynchos
-
inhibits competitively with respect to acetyl-CoA, noncompetitively with respect to malonyl-CoA, and in a mixed manner with respect toNADPH.IC50 = 0.093 mM
additional information
grape skin extract
Gallus gallus
-
IC50 value is 4.61 microg/ml, pH 7.0, 37°C
-
additional information
procyanidin
Homo sapiens
-
IC50 value is 0.087 microg/ml, 37°C, pH not specified in the publication
additional information
resveratrol
Gallus gallus
-
IC50 value is 11.1 microg/ml, pH 7.0, 37°C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
specific activity of recombinant domain I and its subdomains
additional information
-
increase after exposure of animals to cold temperatures for 48 h
additional information
specific malonyl consumption rate is 282 nmol per min per mg protein, pH 7.0, 25°C
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.8
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
30
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
487574, 487575, 487577, 487579, 487580, 487582, 487587, 487589, 487593, 487595, 661027, 661369, 662527, 672604, 720118, 735850
-
-
brenda
-
487574, 487584, 487585, 487592, 663001, 669416, 671025, 671198, 673222, 675586, 676254, 676932, 702058, 703080, 704079, 705999, 706003
-
-
brenda
-
486863, 487569, 487574, 487575, 487576, 487586, 487588, 487594, 661000, 661080, 661434, 661464, 662937, 675103, 705521
-
-
brenda
animals fed with semipurified diets containing either 1% w/w corn oil or 10% each of beef tallow, corn oil, perilla oil, and fish oil. Enzyme activity is reduced in the polyunsaturated fat-fed group in the order of fish oil, perilla oil, and corn oil
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
mammary adenocarcinoma cell, expression of high levels of enzyme
brenda
-
FAS is overexpressed significantly in pathologic and normal mucosa of patients with ulcerative colitis, mainly in the acute phase
brenda
-
oral squamous carcinoma cell lines SCC-4, SCC-9, SCC-15, SCC-25, differential expression of enzyme being highest in SCC-9 followed by SCC-25
brenda
-
at clinically relevant levels, inhibits FASN mRNA, protein expression and enzymatic activity in prostate cancer cells
brenda
-
-
487574, 487575, 487577, 487579, 487580, 487593, 487595, 662527, 661369, 661027, 672604, 720118, 735850
brenda
-
feeding wild-type mice a chow diet supplemented with the natural FXR agonist chenodeoxycholic acid results in a significant induction of FAS mRNA expression
brenda
-
at clinically relevant levels, inhibits FASN mRNA, protein expression and enzymatic activity in prostate cancer cells
brenda
-
positive feedback regulation between AKT activation and fatty acid synthase expression in ovarian carcinoma cells
brenda
-
at clinically relevant levels, inhibits FASN mRNA, protein expression and enzymatic activity in prostate cancer cells
brenda
-
high-level expression of fatty acid synthase in human prostate cancer tissues is linked to activation and nuclear localization of Akt/PKB
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
-
FASII supplies the C8 substrate for lipoic acid synthesis
physiological function
malfunction
-
Fas2 KO strains are unable to form normal biofilms and are more efficiently killed by murine-like macrophages, J774.16, than the wild type, heterozygous and reconstituted strains, Fas2 KO strains are hypersensitive to human serum, and inhibition of Fas2 in wild type Candida parapsilosis by cerulenin significantly decreases fungal growth in human serum
malfunction
mutations in FASN were found in 60 of 631 melanoma samples (9.5%). Patients with mutations exhibit a preferable therapeutic outcome. Ten (9.2%) of 109 patients harbored FASN mutations, and exhibit improved immunotherapeutic survival
physiological function
-
fatty acid synthase is a key enzyme regulating de novo fatty acid synthesis
physiological function
-
the Fas2 gene is essential for fungal growth in fatty acid-free medium, but dispensable in medium with fatty acids
physiological function
-
FASN produces phospholipids for membrane microdomains that accommodate receptor tyrosine kinases including epidermal growth factor-receptor ErbB1 and ErbB2
physiological function
-
mice with fatty acid synthase knockout in the myocardium, FASKard, develop normally, manifest normal resting heart function, and have normal cardiac PPARalpha signaling as well as fatty acid oxidation. Mutant mice decompensate with stress. Most die within 1 h of transverse aortic constriction, probably due to arrhythmia. Voltage clamp measurements of FASKard cardiomyocytes show hyperactivation of L-type calcium channel current that can not be reversed with palmitate supplementation.Ca2+/calmodulin-dependent protein kinase II but not protein kinase A signaling is activated in FASKard hearts, and knockdown of fatty acid synthase in cultured cells activates Ca2+/calmodulin-dependent protein kinase II. In addition to being intolerant of the stress of acute pressure, FASKard hearts are also intolerant of the stress of aging, reflected as persistent CaMKII hyperactivation, progression to dilatation, and premature death by 1 year of age. Ca2+/calmodulin-dependent protein kinase II signaling appears to be pathogenic in FASKard hearts
physiological function
inhibition of FASN in Hep-G2 cells can decrease proliferation and promote apoptosis
Show AA Sequence and Transmembrane Helices (3517 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
450000
additional information
additional information
-
active-site mapping of isolated acetyl/malonyl transferase activity domain
additional information
-
sedimentation coefficients of centrifugation of active enzyme
additional information
-
molecular weight of fragments after proteolytic cleavage
additional information
-
molecular weight of fragments after proteolytic cleavage
additional information
-
molecular weight of fragments after proteolytic cleavage
additional information
-
molecular weight of fragments after proteolytic cleavage
additional information
-
molecular weight of fragments after proteolytic cleavage
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
additional information
dimer
-
2 * 244000, ultracentrifugation in 6 M guanidinium chloride
-
additional information
-
alpha2-dimer of multifunctional subunits: each subunit contains up to seven active centres required for palmitate synthesis and an acyl carrier site, arranged in three domains
additional information
-
alpha2-dimer of multifunctional subunits: each subunit contains up to seven active centres required for palmitate synthesis
additional information
-
alpha2-dimer of multifunctional subunits: each subunit contains up to seven active centres required for palmitate synthesis
additional information
-
alpha2-dimer of multifunctional subunits: each subunit contains up to seven active centres required for palmitate synthesis and an acyl carrier site, arranged in three domains but dimer is the only catalytically active form of fatty acid synthase
additional information
-
alpha2-dimer of multifunctional subunits: each subunit contains up to seven active centres required for palmitate synthesis and an acyl carrier site, arranged in three domains but dimer is the only catalytically active form of fatty acid synthase
additional information
-
fatty acid synthetases of vertebrates and yeast are stable enzyme complexes of multifunctional polypeptide chains, the fatty acid synthetases of plants and Escherichia coli consist of non-associated individual enzymes
additional information
-
structural analysis by electron microscopy, enzyme monomers in the dimeric form adopt a coiled conformation that allows for a variety of intra- and intermonomer functional domain interactions
additional information
-
alpha2-dimer of multifunctional subunits: each subunit contains up to seven active centres required for palmitate synthesis and an acyl carrier site, arranged in three domains but dimer is the only catalytically active form of fatty acid synthase
-
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
-
condensing activities of the Mycobacterium tuberculosis type II fatty acid synthase are differentially regulated by phosphorylation
phosphoprotein
-
condensing activities of the Mycobacterium tuberculosis type II fatty acid synthase are differentially regulated by phosphorylation
-
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
high-resolution crystal structure of a large part of human fatty acid synthase that encompasses the tandem domain of beta-oxoacyl synthase KS connected by a linker domain to the malonyltransferase domain MAT, to 2.15 A resolution. Hinge regions that allow for substantial flexibility of the subdomains are defined. The KS domain forms the canonical dimer, and its substrate-binding site geometry differs markedly from that of bacterial homologues but is similar to that of the porcine orthologue. The didomain structure reveals a possible way to generate a small and compact KS domain by omitting a large part of the linker and MAT domains, which could greatly aid in rapid screening of KS inhibitors. In the crystal, the MAT domain exhibits two closed conformations that differ significantly by rigid-body plasticity
molecular dynamic simulation based binding free energy calculation and access tunnels analysis. The C16 acyl tail fatty acid, the major product of FAS, fits to the active site on beta-ketoacyl synthase domain better than any other substrates. The geometric shape of active site on beta-ketoacyl synthase domain might explain the product ratio of FAS
-
of thioesterase domain, which comprises two dissimilar subdomains A and B
pharmacophore modeling based on crystal structure of 3-oxoacyl-[acyl-carrier-protein] synthase domain, PDB entry 3HHD
three-dimensional map of yeast fatty acid synthase at 5.9 A resolution, obtained by electron cryomicroscopy of single particles. Distinct density regions in the reaction chambers next to each of the catalytic domains fitted the substrate-binding acyl carrier protein domain. In each case, this results in the expected distance of about 18 A from the acyl carrier protein substrate-binding site to the active site of the catalytic domains. The multiple, partially occupied positions of the acyl carrier protein within the reaction chamber provide direct structural insight into the substrate-shuttling mechanism. The acyl carrier protein domain is mobile within the fatty acid synthase barrel, enabling it to visit successive catalytic sites
-
structure at 4.5 A resolution. The dimeric synthase adopts an asymmetric X-shaped conformation with two reaction chambers on each side formed by a full set of enzymatic domains required for fatty acid elongation, which are separated by considerable distances
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D2553A/G2559S/M2600W
-
in addition to G2559S/M2600W, mutation in ketoacyl synthase domain KS, mutation increases the fraction of long chain acyl-CoA produced
D2553N/G2559S/M2600W
-
in addition to G2559S/M2600W, mutation in ketoacyl synthase domain KS, mutation increases the fraction of long chain acyl-CoA produced
D2556A/G2559S/M2600W
-
in addition to G2559S/M2600W, mutation in ketoacyl synthase domain KS, mutation increases the fraction of long chain acyl-CoA produced
G2559S/D2622A/M2600W
-
in addition to G2559S/M2600W, mutation in ketoacyl synthase domain KS, mutant is most efficient in C8-CoA production but impaired in activity
G2559S/M2600W
-
mutant produces produces a bimodal spectrum of C8- and C14/C16-CoA in vitro
G2559S/N2621D/M2600W
-
in addition to G2559S/M2600W, mutation in ketoacyl synthase domain KS, mutant is most efficient in C8-CoA production but impaired in activity
N2557E/G2559S/M2600W
-
in addition to G2559S/M2600W, mutation in ketoacyl synthase domain KS, mutant is most efficient in C8-CoA production but impaired in activity
S36T
-
mutant in acyl carrier protein, mutant is incapable of undergoing phosphopantetheinylation. The S36T mutant is a weaker inhibitor of the fatty acid synthase than holo-acyl carrier protein, suggesting that the prostheticgroup of the acyl carrier protein contributes directly to its inhibitory characteristics at high concentrations
R606A
active site mutant of didomain construct. The specificity constant for malonyl-CoA is 40fold smaller than the wild-type constant
C161Q
-
mutation of ketoacyl synthase, less conformational variability than wild-type
C161T
-
defective in beta-ketoacyl synthase, no overall fatty acid synthase activity
G1888A
K326A
R1508A
-
similar activity as wild-type in overall reaction, analysis of partial reactions
R1508D
-
14% of wild-type activity in overall reaction, analysis of partial reactions
R1508K
-
58% of wild-type activity in overall reaction, analysis of partial reactions
R606A
-
reduced malonyl/acetyltransferase activity, increased transacylase activity, 16000fold increased selectivity for acetyl-CoA, 8.5fold increase of Km for malonyl-CoA
R606K
-
reduced malonyl/acetyltransferase activity, increased transacylase activity, 16fold increased selectivity for acetyl-CoA
S2302A
-
mutation of thioesterase, less conformational variability than wild-type
additional information
G1888A
-
mutation of beta-ketoacyl reductase, less conformational variability than wild-type
K326A
-
defective in beta-ketoacyl synthase, no overall fatty acid synthase activity
K326A
-
mutation of ketoacyl synthase, less conformational variability than wild-type
additional information
-
enzyme knockout mutants, heterozygous mutant animals are ostensibly normal, with about 50% reduction in enzyme mRNA and 35% reduction in enzyme activity. Partial haploid insufficieny in heterozygous animals, most embryos die at various stages of development. No production of enzyme homozygous mutant animals
additional information
dissection of the enzyme into condensing, processing and terminating parts, engineering and reassembly to generate new polyketide synthase-like modules as well as bimodular constructs. The reengineered modules resemble all four common types of polyketide synthases
additional information
expression of a didomain subconstruct KS-MAT (2?853), bearing a beto-ketoacyl synthase KS knockout C161G and malonyl/acetyltransferase MAT
additional information
-
engineering of a enzyme containing one wild-type subunit and one subunit comprised by mutations in all seven functional domains. Mutant enzyme is active
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
50% loss of activity in dilute, mildly alkaline solution within 3.5 h, high ionic strength together with DTT reactivates
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
dissociation of native enzyme leads to loss of activity
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ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
0C, inactivation after 12 h, reactivation after 2 h at 25C in the presence of NADPH, not acetyl-CoA or NADH
4°C, 90% loss of activity in 8 days with 40% dissociation of native enzyme, incubation at 38°C with 10 mM DTT restores activity
-
0C, inactivation after 12 h, reactivation after 2 h at 25C in the presence of NADPH, not acetyl-CoA or NADH
-
0C, inactivation after 12 h, reactivation after 2 h at 25C in the presence of NADPH, not acetyl-CoA or NADH
-
0C, inactivation after 12 h, reactivation after 2 h at 25C in the presence of NADPH, not acetyl-CoA or NADH
-
0C, inactivation after 12 h, reactivation after 2 h at 25C in the presence of NADPH, not acetyl-CoA or NADH
-
0C, inactivation after 12 h, reactivation after 2 h at 25C in the presence of NADPH, not acetyl-CoA or NADH
-
0C, inactivation after 12 h, reactivation after 2 h at 25C in the presence of NADPH, not acetyl-CoA or NADH
-
0C, inactivation after 12 h, reactivation after 2 h at 25C in the presence of NADPH, not acetyl-CoA or NADH
-
0C, inactivation after 12 h, reactivation after 2 h at 25C in the presence of NADPH, not acetyl-CoA or NADH
-
0C, inactivation after 12 h, reactivation after 2 h at 25C in the presence of NADPH, not acetyl-CoA or NADH
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
domain I with acetyl and malonyl transacetylase activity and beta-hydroxyacyl dehydratase activity after expression in E. coli
-
homogeneity
purification of 2 structurally related but functionally differentiated fatty acid synthases: FAS-A and FAS-B, homogeneity
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
domain I with acetyl and malonyl transacetylase activity and beta-hydroxyacyl dehydratase activity
-
expressed in Saccharomyces cerevisiae oar1DELTA cells
individual overexpression of all components of fatty acid synthase in Escherichia coli
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
(10E,12Z)-octadec-10,12-dienoic acid downregulates FAS expression in a concnetration-dependent manner, while (9Z,11E)-octadec-9,11-dienoic acid has no effect. (10E,12Z)-octadec-10,12-dienoic acid at 0.05 mM decreases FAS expression in MCF-7 cells by 52%, at 0.1 mM (10E,12Z)-octadec-10,12-dienoic acid, FAS protein is downregulated in MCF-7 (80%), LnCaP (27%), and HT-29 (61%) cells
-
C75 downregulates FASN mRNA in A2780 with an IC50 after 3d of 0.00525 mg/ml and an IT50 (time required for 50% inhibition) at 0.007 mg/ml of 21.5 h. This corresponds with FASN protein downregulation (IC50 = 0.00415 mg/ml), although the dynamics are slower (IT50 = 40 h). Pelitinib, given for 3d, abrogates FASN mRNA and protein in A-2780 cellsat doses as low as 0.003 mM
-
expression of Fas1 and Fas2 is significantly elevated by the presence of glucose
-
FAS expression is reduced by 25% in Ki-ras-induced actin-interacting protein-deficient liver
-
hepatic fatty acid synthase activity is significantly higher after week 1 of refeeding
-
isoleucine, whey, leucine, valine, skim milk, and casein downregulate the expression of fatty acid synthase in a concentration-dependent manner, a plateau is reached at 1.0% (w/v) skim milk and casein corresponding to about 40% inhibition of FAS expression, whey leads to 54% inhibition of FAS expression at 2.0%(w/v)
-
mithramycin inhibits FAS expression, transfection of transcription factor Sp1 siRNA suppresses FAS expression
-
oleic acid and Tween 80 downregulate the expression of the fatty acid synthase while myristic acid, stearic acid, and Tween 40 do not
-
relative FASN mRNA expression is upregulated by 9 and 5fold, respectively, for high-concentrate diet (85% concentrate: 15% roughage) and diet on endophyte-free tall fescue pastures with corn grain supplement compared with pasture diet, grain feeding upregulates FASN mRNA expression
-
the stromal cell-derived factor-1 alpha/CXCR4 axis induces the expression of fatty acid synthase via sterol regulatory element binding protein-1 activation in cancer cells. Sterol regulatory element-binding protein-1 is a major modulator of fatty acid synthase transcription. Also recombinant stromal cell-derived factor-1 alpha-induced phosphatidylinositol-3'-kinase/protein kinase B (Akt) phosphorylation is involved in the expression or activities of fatty acid synthase
-
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
reconstitution of fatty acid synthase using purified protein components. When all ketosynthases are present at 1 microM, the maximum rate of free fatty acid synthesis of the fatty acid synthase exceeds 100 microM/min. The steady-state turnover frequency is not significantly inhibited at high concentrations of any substrate or cofactor. Fatty acid synthase activity is saturated with respect to most individual protein components when their concentrations exceeded 1 microM. The exceptions are protein components FabI and FabZ, which increase fatty acid synthase activity up to concentrations of 10 microM, FabH and FabF, which decrease fatty acid synthase activity at concentrations higher than 1 microM, and holo-acyl carrier protein and TesA, which give maximum fatty acid synthase activity at 30 microM concentrations
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
medicine
nutrition
-
animals fed with semipurified diets containing either 1% w/w corn oil or 10% each of beef tallow, corn oil, perilla oil, and fish oil. Enzyme activity is reduced in the polyunsaturated fat-fed group in the order of fish oil, perilla oil, and corn oil
analysis
-
targeted liquid chromatography-mass spectroscopy method to directly measure endogenous levels of malonyl-CoA to drive a drug development structure-activity relationship screening cascade. The assay is amenable to multiplexing cellular endpoints, has a typical Z' of >0.6, and has high reproducibility of EC50 values
analysis
simple mass spectrometry-based assay that affords monitoring of FASN activity and its product specificity. Purified FASN is incubated with 13C-labeled malonyl-CoA, acetyl-CoA, and NADPH, at defined time points the reaction mixture is spiked with an internal non-esterified palmitic acid standard and extracted, and the extract is analyzed directly, without vacuum evaporation and chemical derivatization, by direct-infusion high-resolution mass spectrometry in negative ion mode. The assay supports essentially noise-free detection and absolute quantification of de novo synthetized 13C-labeled non-esterified fatty acids
medicine
-
anorectic effect of C75 is independent of its inhibition of enzyme in the hypothalamus
medicine
-
androgen-independent expression of enzyme in oral SSC cells, enzyme activity is necessary for their proliferation
medicine
-
in cancer cells, enzyme plays a major role in the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains. Link between enzyme overexpression and dysregulation of membrane composition and functioning in tumor cells
medicine
-
triclosan suppresses mammary carcinogenesis by inhibiting enzyme
medicine
-
TRAMP mouse prostate adenocarcinoma cells show high enzyme expression and activity compared to nontransgenic littermates. Inhibition of enzyme expression and activity results in dose-dependent reduction in cell survival
medicine
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FAS is a target for drug development against obesity and related diseases, and FAS inhibitors have antitumor activity
medicine
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FAS could be a useful signal for early detection of ulcerative coliti
medicine
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the enzyme is a potential therapeutic target to treat cancer and obesity. Acylphloroglucinol derivatives could be considered to be a promising class of FAS inhibitors
medicine
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fatty acid synthase-dependent palmitoylation of epidermal growth factor receptor is required for epidermal growth factor receptor dimerization and kinase activation. Inhibition of fatty acid synthase or palmitoyl acyltransferases reduces the activity and down-regulated the levels of epidermal growth factor receptor, and sensitizes cancer cells to epidermal growth factor receptor tyrosine kinase inhibitors
medicine
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endogenously synthesized fatty acids do not fulfill a specific function in cancer cells. Cancer cells do not produce fatty acids that are different from those derived from exogenous palmitate, these fatty acids are esterified to the same lipid and phospholipid classes in the same proportions, and their distribution within neutral lipids is not different from untransformed cells. Anoxia increases glycolysis 2-3fold, with no concomitant increase in lipogenesis
medicine
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fatty acid synthase expression, which is upregulated in many human cancers, causes resistance to multiple anticancer drugs via inhibiting drug-induced ceramide production, caspase 8 activation, and apoptosis. Fatty acid synthase overexpression suppresses tumor necrosis factor-alpha production and nuclear factor-kappaB activation as well as drug-induced activation of neutral sphingomyelinase
medicine
inhibition of FASN suppresses the cell survival of Hep-G2 cells by inhibiting the beta-catenin/C-myc pathway
medicine
FASN may act as a key targetable metabolic regulator of glucose-induced epidermal growth factor receptor (EGFR) oncogenic signaling in oral potentially malignant disorders. Oral dysplastic keratinocytes exposed to high glucose show EGFR activation in a FASN-dependent manner. High glucose significantly enhances cell viability and migration in a FASN/EGFR-mediated fashion
medicine
in melanoma and non-small cell lung cancer patients, FASN mutations associate with a preferable immunotherapeutic prognosis and response rate. A favorable tumor immunogenicity and immune microenvironment are involved in FASN mutations
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Release 2026.1 (March 2026)
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