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Information on EC 2.3.1.221 - noranthrone synthase and Organism(s) Aspergillus parasiticus and UniProt Accession Q12053

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EC Tree
     2 Transferases
         2.3 Acyltransferases
             2.3.1 Transferring groups other than aminoacyl groups
                2.3.1.221 noranthrone synthase
IUBMB Comments
A multi-domain polyketide synthase involved in the synthesis of aflatoxins in the fungus Aspergillus parasiticus. The hexanoyl starter unit is provided to the acyl-carrier protein (ACP) domain by a dedicated fungal fatty acid synthase .
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Aspergillus parasiticus
UNIPROT: Q12053
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Word Map
The taxonomic range for the selected organisms is: Aspergillus parasiticus
The enzyme appears in selected viruses and cellular organisms
Synonyms
polyketide synthase a, norsolorinic acid anthrone-producing polyketide synthase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
norsolorinic acid anthrone synthase
-
-
norsolorinic acid anthrone-producing polyketide synthase
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-
polyketide synthase A
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-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
7 malonyl-CoA + hexanoyl-[acyl-carrier protein] = 7 CoA + norsolorinic acid anthrone + [acyl-carrier protein] + 7 CO2 + 2 H2O
show the reaction diagram
SYSTEMATIC NAME
IUBMB Comments
malonyl-CoA:hexanoate malonyltransferase (norsolorinic acid anthrone-forming)
A multi-domain polyketide synthase involved in the synthesis of aflatoxins in the fungus Aspergillus parasiticus. The hexanoyl starter unit is provided to the acyl-carrier protein (ACP) domain by a dedicated fungal fatty acid synthase [1].
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
7 malonyl-CoA + acetyl-[acyl-carrier protein]
?
show the reaction diagram
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-
-
-
?
7 malonyl-CoA + hexanoyl-[acyl-carrier protein]
7 CoA + norsolorinic acid anthrone + [acyl-carrier protein] + 7 CO2 + 2 H2O
show the reaction diagram
additional information
?
-
-
processivity of polyketide extension and substrate specificity, overview. The enzyme shows activity against hexanoyl- and acetyl-, but not malonyl-CoA. Rapid loading of extension units onto the carrier domain facilitates efficient chain extension in a manner kinetically favorable to ultimate product formation. Essential roles of the product template and thioesterase domains for cyclization and product release, editing role for the thioesterase domain
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
7 malonyl-CoA + hexanoyl-[acyl-carrier protein]
7 CoA + norsolorinic acid anthrone + [acyl-carrier protein] + 7 CO2 + 2 H2O
show the reaction diagram
-
-
-
-
?
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
15.38
acetyl-[acyl-carrier protein]
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pH 7.0, 22°C
1.46
hexanoyl-[acyl-carrier protein]
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pH 7.0, 22°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0407
acetyl-[acyl-carrier protein]
-
pH 7.0, 22°C
0.0472
hexanoyl-[acyl-carrier protein]
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pH 7.0, 22°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0026
acetyl-[acyl-carrier protein]
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pH 7.0, 22°C
0.032
hexanoyl-[acyl-carrier protein]
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pH 7.0, 22°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
-
assay at room temperature
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene pksA
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
the pksA gene is located in the aflatoxin pathway gene cluster and is linked to the nor-1 gene, an aflatoxin pathway gene required for converting norsolorinic acid to averantin
malfunction
strain SRRC 2043 is a disruption mutant defective in the pksA locus. Disruption of pksA results in an inability to produce aflatoxin intermediates
metabolism
pksA is a polyketide synthase gene required for the early steps of aflatoxin biosynthesis
metabolism
physiological function
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PksA, which initiates biosynthesis of the environmental carcinogen aflatoxin B1, is one of the multidomain iterative polyketide synthases, IPKSs
additional information
-
the enzyme also has an editing function for the C-terminal thioesterase domain beyond its synthetic role in Claisen/Dieckmann cyclization and product release. Domain architecture and expected enzyme-bound intermediates of PksA, overview
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
S1937A
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inactive mutant
additional information
construction of strain SRRC 2043, a disruption mutant defective in the pksA locus
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant C- or N-terminally His6-tagged mono-, di-, and tridomains protein fragments from Escherichia coli by metal affinity cromatography
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recombinant N-terminally His6-tagged enzyme domains from Escherichia coli strain BL21(DE3)
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recombinant wild-type and mutant proteins from Escherichia coli strains BL21(DE3) or Rosetta2(DE3)
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene pksA, DNA and amino acid sequence determination and analysis
expression of N-terminally His6-tagged enzyme domains in Escherichia coli strain BL21(DE3)
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expression of wild-type and mutant proteins in Escherichia coli strains BL21(DE3) or Rosetta2(DE3)
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gene pksA, cloning of various mono-, di-, and tridomains for combinatorial reconstitution experiments, expression of the either C- or N-terminally His6-tagged protein fragments in Escherichia coli
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Crawford, J.M.; Thomas, P.M.; Scheerer, J.R.; Vagstad, A.L.; Kelleher, N.L.; Townsend, C.A.
Deconstruction of iterative multidomain polyketide synthase function
Science
320
243-246
2008
Aspergillus parasiticus
Manually annotated by BRENDA team
Vagstad, A.L.; Bumpus, S.B.; Belecki, K.; Kelleher, N.L.; Townsend, C.A.
Interrogation of global active site occupancy of a fungal iterative polyketide synthase reveals strategies for maintaining biosynthetic fidelity
J. Am. Chem. Soc.
134
6865-6877
2012
Aspergillus parasiticus
Manually annotated by BRENDA team
Chang, P.K.; Cary, J.W.; Yu, J.; Bhatnagar, D.; Cleveland, T.E.
The Aspergillus parasiticus polyketide synthase gene pksA, a homolog of Aspergillus nidulans wA, is required for aflatoxin B1 biosynthesis
Mol. Gen. Genet.
248
270-277
1995
Aspergillus parasiticus (Q12053), Aspergillus parasiticus SRRC 2043 / RHN1 (Q12053)
Manually annotated by BRENDA team
Crawford, J.M.; Korman, T.P.; Labonte, J.W.; Vagstad, A.L.; Hill, E.A.; Kamari-Bidkorpeh, O.; Tsai, S.C.; Townsend, C.A.
Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization
Nature
461
1139-1143
2009
Aspergillus parasiticus
Manually annotated by BRENDA team