Information on EC 2.3.1.85 - fatty-acid synthase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
2.3.1.85
-
RECOMMENDED NAME
GeneOntology No.
fatty-acid synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acyl group transfer
-
-
-
-
decarboxylation
-
-
-
-
redox reaction
-
-
-
-
thioester hydrolysis
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
(5Z)-dodec-5-enoate biosynthesis
-
-
Fatty acid biosynthesis
-
-
fatty acid biosynthesis (plant mitochondria)
-
-
fatty acid biosynthesis initiation I
-
-
fatty acid biosynthesis initiation II
-
-
fatty acid biosynthesis initiation III
-
-
fatty acid elongation -- saturated
-
-
Metabolic pathways
-
-
octanoyl-[acyl-carrier protein] biosynthesis (mitochondria, yeast)
-
-
oleate biosynthesis IV (anaerobic)
-
-
palmitate biosynthesis I (animals and fungi)
-
-
palmitate biosynthesis II (bacteria and plants)
-
-
superpathway of fatty acid biosynthesis initiation (E. coli)
-
-
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 3-oxoacyl-[acyl-carrier-protein] synthase, 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.
CAS REGISTRY NUMBER
COMMENTARY hide
9045-77-6
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
goose
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
goat, female
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
male FVB-N
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
Sprague-Dawley
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
metabolism
-
FASII supplies the C8 substrate for lipoic acid synthesis
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
show the reaction diagram
acetyl-CoA + malonyl-CoA + NADH
palmitate + CoA + CO2 + NAD+
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14 H+
palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6 H2O
show the reaction diagram
additional information
?
-
-
enzyme generated signals are needed to support preadipocyte differentiation
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4'-phosphopantetheine
NADH
-
requirement, 10% as effective as NADPH
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(+)-catechin
-
50% inhibition of overall enzyme reaction at 1.6 mM, 50% inhibition of ketoacyl reduction reaction at 7.4 mM
(+-)-taxifolin
-
50% inhibition at 0.041163 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
(9Z,11E)-octadec-9,11-dienoic acid
-
-
1,1'-[methanediylbis(2,4,6-trihydroxy-5-methylbenzene-3,1-diyl)]dibutan-1-one
-
IC50: 0.0254 mM
1,3-Dibromo-2-propanone
1-(2,6-dihydroxy-4-methoxy-3-methylphenyl)butan-1-one
-
IC50: 0.0491 mM
2,2'-methanediylbis(3,5-dihydroxy-4,4-dimethyl-6-propanoylcyclohexa-2,5-dien-1-one)
-
IC50: 0.0602 mM
2,3-Butanedione
-
-
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-oxooctanoyl-CoA
-
competitively inhibits malonyl-transferase reaction
4',6,7-trihydroxylisoflavone
-
IC50: 0.0295 mM
5-chloropyrazinamide
-
IC50: 0.151 mM
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
apigenin
-
IC50: 0.0176 mM
aryl-acyl-beta-alanyl NADP+
-
inhibits beta-ketoacyl-reductase
-
avicularin
-
IC50: 0.00615 mM
baicalein
-
50% inhibition at 0.11169 mM
Benzamide
-
100 mM, 15% inhibition
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
cerulenin
Chloroacetyl-CoA
-
-
CoA
-
competitive inhibition
crotonyl-CoA
-
dehydrase activity
daidzein
-
IC50: 0.0732 mM
diisopropylfluorophosphate
dutasteride
-
at clinically relevant levels, inhibits FASN mRNA, protein expression and enzymatic activity in prostate cancer cells
epigallocatechin-3-gallate
-
-
fisetin
-
50% inhibition at 0.01877 mM
galangin
gallic acid
-
50% inhibition of overall enzyme reaction at 21 mM, 50% inhibition of ketoacyl reduction reaction at 26 mM
genistein
-
0.0287 mM
ginkgolic acid C15:1
ginkgolic acid C17:1
ginkgolic acid C17:2
hesperetin
-
50% inhibition at 0.06886 mM
hyperoside
-
IC50: 0.0746 mM
iodoacetamide
iso-liquiritigenin
-
IC50: 0.0088 mM
isoquercitrin
-
IC50: 0.108 mM
kaempferol
long-chain acyl-CoA
-
malonyl-transferase reaction
luteolin
Malonyl pantetheine
-
malonyl-transferase reaction
malonyl-CoA
-
competitive, malonyl-transferase reaction
morin
-
50% inhibition at 0.00233 mM
myricetin
-
50% inhibition at 0.02718 mM
N-ethylmaleimide
-
inhibition of elongation process and malonyl transfer at 10 mM
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
Octanoyl-CoA
-
competitively inhibits malonyl-transferase reaction
Phenylglyoxal
-
-
phloretin
-
0.0261 mM
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
-
Pyrazinamide
-
IC50: 8.9 mM
pyridoxal 5'-phosphate
quercetin
quercitrin
-
IC50: 0.0456 mM
resveratrol
-
IC50: 0.0085 mM
S-(4-Bromo-2,3-dioxobutyl)-CoA
sodium dodecylsulfate
-
causes conformational changes at higher concentrations
taxifolin
-
-
tetrahydrolipstatin
-
i.e. orlistat
trans-4-carboxy-5-octyl-3-methylenebutyrolactone
-
-
triclosan
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
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0005 - 0.008
acetyl-CoA
0.001 - 0.1
malonyl-CoA
0.121
NADH
-
wild-type, enoylreductase activity
0.0041 - 2.7
NADPH
additional information
additional information
-
Km-values for various partial activities of fatty acid synthetase
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0317 - 2.7
acetyl-CoA
0.0002 - 2.7
malonyl-CoA
0.12 - 1.1
NADH
1.1 - 73
NADPH
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.055 - 0.059
5-chloropyrazinamide
-
37C, pH 7.4
0.02
CoA
-
-
0.0012 - 0.0098
luteolin
1.04
Malonyl pantetheine
-
-
0.00205 - 0.00357
morin
2.6
Pyrazinamide
-
37C, pH 7.4
0.00183 - 0.00301
quercetin
0.14
sodium dodecylsulfate
-
-
0.02053 - 0.094
taxifolin
210 - 580
Urea
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0254
1,1'-[methanediylbis(2,4,6-trihydroxy-5-methylbenzene-3,1-diyl)]dibutan-1-one
Gallus gallus
-
IC50: 0.0254 mM
0.0491
1-(2,6-dihydroxy-4-methoxy-3-methylphenyl)butan-1-one
Gallus gallus
-
IC50: 0.0491 mM
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
0.0295
4',6,7-trihydroxylisoflavone
Anas platyrhynchos
-
IC50: 0.0295 mM
0.151
5-chloropyrazinamide
Mycobacterium tuberculosis
-
IC50: 0.151 mM
0.0176
apigenin
Anas platyrhynchos
-
IC50: 0.0176 mM
0.00615
avicularin
Anas platyrhynchos
-
IC50: 0.00615 mM
0.013
cerulenin
Gallus gallus
-
pH 7.0, 37C
0.0732
daidzein
Anas platyrhynchos
-
IC50: 0.0732 mM
0.017
ginkgolic acid C15:1
Gallus gallus
-
pH 7.0, 37C
0.01
ginkgolic acid C17:1
Gallus gallus
-
pH 7.0, 37C
0.009
ginkgolic acid C17:2
Gallus gallus
-
pH 7.0, 37C
0.0746
hyperoside
Anas platyrhynchos
-
IC50: 0.0746 mM
0.0088
iso-liquiritigenin
Anas platyrhynchos
-
IC50: 0.0088 mM
0.108
isoquercitrin
Anas platyrhynchos
-
IC50: 0.108 mM
0.062
luteolin
Gallus gallus
-
pH 7.0, 37C
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
8.9
Pyrazinamide
Mycobacterium tuberculosis
-
IC50: 8.9 mM
0.0456
quercitrin
Anas platyrhynchos
-
IC50: 0.0456 mM
0.0085
resveratrol
Anas platyrhynchos
-
IC50: 0.0085 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.015
-
for malonyl-CoA, R606A mutant
0.078 - 0.1
-
palmitate
0.14 - 0.16
-
-
0.154
-
for malonyl-CoA, R606K mutant
0.6
-
NADPH
1.12 - 1.4
-
NADPH, 30C
1.13 - 2.77
-
various tagged wild-type enzyme
1.2 - 1.6
-
NADPH
1.3
-
NADPH
1.61
-
for malonyl-CoA, wild-type enzyme
2.049
-
wild-type enzyme, activity in mutants is less than 0.5%
2.6
-
NADPH
2.68
-
for acetyl-CoA, wild-type enzyme
4.53
-
for acetyl-CoA, R606K mutant
17.8
-
for acetyl-CoA, R606A mutant
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 6.7
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
mammary adenocarcinoma cell, expression of high levels of enzyme
Manually annotated by BRENDA team
-
FAS is overexpressed significantly in pathologic and normal mucosa of patients with ulcerative colitis, mainly in the acute phase
Manually annotated by BRENDA team
-
at clinically relevant levels, inhibits FASN mRNA, protein expression and enzymatic activity in prostate cancer cells
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
at clinically relevant levels, inhibits FASN mRNA, protein expression and enzymatic activity in prostate cancer cells
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
236000
-
SDS-PAGE
265000
-
SDS-PAGE
270000
-
subunit, SDS-PAGE
272000
-
SDS-PAGE
272500
-
calculated from nucleotide sequence
310000
-
SDS-PAGE
324900
-
calculated from nucleotide sequence
400000
-
value above 400000 Da, polymer, SDS-PAGE
425000
-
sedimentation equilibrium method
431000
-
calculated from amino acid sequence
434000
-
ultracentrifugation in 0.5-0.8 M phosphate buffer
450000
480000
-
SDS-PAGE
additional information
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hexamer
-
homohexamer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
condensing activities of the Mycobacterium tuberculosis type II fatty acid synthase are differentially regulated by phosphorylation
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
-
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
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.4
-
inactivation, decreased by 0.2 M KCl or 0.02 mM NADP(H)
487575
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
50% loss of activity in dilute, mildly alkaline solution within 3.5 h, high ionic strength together with DTT reactivates
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
dissociation of native enzyme leads to loss of activity
dithiothreitol stabilizes
-
foaming leads to surface inactivation
-
low ionic strength leads to dissociation of native enzyme and inactivation
-
phosphate buffer, 0.5 M, reassociates enzyme subunits
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
acetonitrile
-
up to 10% v/v, stable to
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, at least a month in the presence of DTT
-
-20C, under nitrogen at least 1-2 months
-
0C, inactivation after 12 h, reactivation after 2 h at 25C in the presence of NADPH, not acetyl-CoA or NADH
4C, 90% loss of activity in 8 days with 40% dissociation of native enzyme, incubation at 38C with 10 mM DTT restores activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 beta-ketoacyl reductase containing fragments after sequential proteolysis
-
680fold, erythrocyte enzyme immunologically not related to liver enzyme
-
95% pure, transacyclase domain
-
domain I with acetyl and malonyl transacetylase activity and beta-hydroxyacyl dehydratase activity after expression in E. coli
-
fusion protein with maltose-binding protein
-
homogeneity
isolation of modified dimers containing independently mutated subunits
-
near homogeneity
-
partial
-
purification of 2 structurally related but functionally differentiated fatty acid synthases: FAS-A and FAS-B, homogeneity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
domain I with acetyl and malonyl transacetylase activity and beta-hydroxyacyl dehydratase activity
-
expressed in Saccharomyces cerevisiae oar1DELTA cells
full length cDNA, cDNA encoding domain I and cDNA encoding domains II and III
-
gene sequences
-
individual overexpression of all components of fatty acid synthase in Escherichia coli
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transacyclase domain
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wild-type and mutant enzymes are expressed in Sf9 cells
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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
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17beta-estradiol increases FAS expression, estrogen induces FAS expression
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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
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expression of Fas1 and Fas2 is significantly elevated by the presence of glucose
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FAS expression is reduced by 25% in Ki-ras-induced actin-interacting protein-deficient liver
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fatty acid synthase is overexpressed in ovarian cancer
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hepatic fatty acid synthase activity is significantly higher after week 1 of refeeding
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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)
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mithramycin inhibits FAS expression, transfection of transcription factor Sp1 siRNA suppresses FAS expression
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oleic acid and Tween 80 downregulate the expression of the fatty acid synthase while myristic acid, stearic acid, and Tween 40 do not
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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
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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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transcription factor Sp3 and Sp4 siRNAs do not affect FAS expression
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
S36T
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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
A2419L
97% reduction of thioesterase activity
A2419M
92% reduction of thioesterase activity
F2371W
20% reduction of thioesterase activity
F2423A
67% reduction of thioesterase activity
F2423W
24% reduction of thioesterase activity
I2250W
97% reduction of thioesterase activity
K1699A
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specific activity is 10% of wild-type value
K1699Q
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specific activity is 7.5% of wild-type value
K2426A
99% reduction of thioesterase activity
S2151A
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inactive enzyme
S2422A
7% reduction of thioesterase activity
C161A
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no beta-ketoacyl synthase activity
C161Q
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mutation of ketoacyl synthase, less conformational variability than wild-type
C161T
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defective in beta-ketoacyl synthase, no overall fatty acid synthase activity
G1886F
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beta-ketoreductase activity, 130fold increase in Km-value
G1888A
R1508A
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similar activity as wild-type in overall reaction, analysis of partial reactions
R1508D
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14% of wild-type activity in overall reaction, analysis of partial reactions
R1508K
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58% of wild-type activity in overall reaction, analysis of partial reactions
R606A
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reduced malonyl/acetyltransferase activity, increased transacylase activity, 16000fold increased selectivity for acetyl-CoA, 8.5fold increase of Km for malonyl-CoA
R606K
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reduced malonyl/acetyltransferase activity, increased transacylase activity, 16fold increased selectivity for acetyl-CoA
S215A
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defective in acyl carrier protein
S2302A
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mutation of thioesterase, less conformational variability than wild-type
S518A
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no malonyl/acetyltransferase activity
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
complete renaturation of enzyme inactivated by Zn2+ using dithiothreitol
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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 hide
LITERATURE
medicine
nutrition
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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
Show AA Sequence (103 entries)
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