Information on EC 2.3.1.194 - acetoacetyl-CoA synthase

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

EC NUMBER
COMMENTARY hide
2.3.1.194
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RECOMMENDED NAME
GeneOntology No.
acetoacetyl-CoA synthase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
acetyl-CoA + malonyl-CoA = acetoacetyl-CoA + CoA + CO2
show the reaction diagram
SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:malonyl-CoA C-acyltransferase (decarboxylating)
The enzyme from the soil bacterium Streptomyces sp. CL190 produces acetoacetyl-CoA to be used for mevalonate production via the mevalonate pathway. Unlike the homologous EC 2.3.1.180 (beta-ketoacyl-[acyl-carrier-protein] synthase III), this enzyme does not accept malonyl-[acyl-carrier-protein] as a substrate.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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-
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Manually annotated by BRENDA team
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Uniprot
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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knockdown of AACS in primary neurons caused decreases in the expression of MAP-2 and NeuN, which are markers of neuronal differentiation, as well as synaptopodin, a marker of spine apparatus
metabolism
physiological function
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acetoacetyl-CoA synthetase is a ketone body-utilizing enzyme for the synthesis of cholesterol and fatty acids, regulation of AACS during neurite outgrowth and physiological role of AACS in neurogenesis, overview. AACS is regulated by SREBP-2 and involved in the normal development of neurons
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 malonyl-CoA
acetoacetyl-CoA + CoA + 2 CO2
show the reaction diagram
acetyl-CoA + malonyl-CoA
acetoacetyl-CoA + CoA + CO2
show the reaction diagram
acetyl-CoA + malonyl-CoA
CoA + acetoacetyl-CoA + CO2
show the reaction diagram
additional information
?
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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 + malonyl-CoA
acetoacetyl-CoA + CoA + CO2
show the reaction diagram
acetyl-CoA + malonyl-CoA
CoA + acetoacetyl-CoA + CO2
show the reaction diagram
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.068
acetyl-CoA
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pH 8.0, 25C; pH 8.0, 30C, reaction with acetyl-CoA and malonyl-CoA
0.028
malonyl-CoA
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pH 8.0, 25C; pH 8.0, 30C, reaction with acetyl-CoA and malonyl-CoA; pH 8.0, 30C, reaction with malonyl-CoA, without acetyl-CoA
additional information
additional information
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steady-state kinetics
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.23
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recombinant mutant H256A, pH 8.0, 25C
8.9
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recombinant His8-tagged wild-type enzyme, pH 8.0, 25C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
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assay at
30
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assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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high enzyme expression level
Manually annotated by BRENDA team
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expression of AACS in the brains of mouse embryos is dramatically increased between E16.5 and E18.5
Manually annotated by BRENDA team
prenatal nicotine exposure leads to decreased expression and increased DNA methylation in the proximal promoter of acetoacetyl-CoA synthetase
Manually annotated by BRENDA team
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mRNA levels and the expression of AACS are increased during neurite outgrowth
Manually annotated by BRENDA team
additional information
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AACS expression analysis during development, overview
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37000
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2 * 37000, recombinant N-terminally His8-tagged enzyme, SDS-PAGE; 2 * 37000, SDS-PAGE
63000
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gel filtration; recombinant N-terminally His8-tagged enzyme, gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
AACS expression analysis during development, overview
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co-expression of polyhydroxyalkanoate synthase, PhaC, from Ralstonia eutropha with acetoacetyl-CoA synthetase in Escherichia coli and Corynebacterium glutamicum leading to enhanced production of polyhydroxybutanoates, by cloning the AACS gene into the phaABC operon of Ralstonia eutropha. Overexpression of AACS leads to a great enhancement of the malonyl-CoA pool in Escherichia coli; recombinant expression of AACS in Corynebacterium glutamicum and Escherichia coli leads to aquired ability to form poly(3-hydroxybutyrate) in the transformed organisms by 19.7 wt% and 10.5 wt%, respectively, biosynthetic pathway, overview
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gene nphT7, organized in the mevalonate pathway gene cluster, functional expression in Streptomyces albus, overexpression of N-terminally His8-tagged enzyme in Escherichia coli; overexpressed in Escherichia coli as an N-terminal His8-tagged protein
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
SREBP-2, a key transcription factor of cholesterol synthesis, interacts with the AACS promoter and is increased during neurite outgrowth, and knockdown of SREBP-2 down-regulates the mRNA levels of AACS in Neuro-2a cells
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C115A
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consumption of malonyl-CoA and an increase in acetyl-CoA. No formation of CoA or acetoacetyl-CoA. C115A mutant enzyme yields acetyl-CoA via its malonyl-CoA decarboxylation activity, presumably by the His256 and Asn286 residues, while it has lost its condensation activity; site-directed mutagenesis, the mutant cleaves malonyl-CoA into acetyl-CoA, but does not form CoA or acetoacetyl-CoA. C115A mutant enzyme yields acetyl-CoA via its malonyl-CoA decarboxylation activity, presumably by the His256 and Asn286 residues, while it has lost its condensation activity
H256A
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can not ve obtained as a soluble protein; site-directed mutagenesis, the mutant enzyme exhibits acetoacetyl-CoA synthesizing activity, but its specific activity is approximately 40fold lower than that of wild-type NphT7
N286A
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site-directed mutagenesis, the mutant cannot be produced recombionantly as a soluble protein; this mutant enzyme exhibits detectable acetoacetyl-CoA synthesizing activity, but its specific is approximately 40fold lower than that of wild-type NphT7
C115A
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consumption of malonyl-CoA and an increase in acetyl-CoA. No formation of CoA or acetoacetyl-CoA. C115A mutant enzyme yields acetyl-CoA via its malonyl-CoA decarboxylation activity, presumably by the His256 and Asn286 residues, while it has lost its condensation activity; site-directed mutagenesis, the mutant cleaves malonyl-CoA into acetyl-CoA, but does not form CoA or acetoacetyl-CoA. C115A mutant enzyme yields acetyl-CoA via its malonyl-CoA decarboxylation activity, presumably by the His256 and Asn286 residues, while it has lost its condensation activity
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H256A
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can not ve obtained as a soluble protein; site-directed mutagenesis, the mutant enzyme exhibits acetoacetyl-CoA synthesizing activity, but its specific activity is approximately 40fold lower than that of wild-type NphT7
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N286A
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this mutant enzyme exhibits detectable acetoacetyl-CoA synthesizing activity, but its specific is approximately 40fold lower than that of wild-type NphT7
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
histological changes, decreased steroid hormone concentrations and decreased cholesterol supply are observed in nicotine-treated fetal adrenals. The expression of genes regulating ketone metabolic process decreases in nicotine-treated fetal adrenals. Acetoacetyl-CoA synthetase (AACS), the enzyme utilizing ketones for cholesterol supply, displays decreased expression and increased DNA methylation in the proximal promoter of AACS
synthesis