Information on EC 2.3.1.238 - monacolin J acid methylbutanoate transferase

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The expected taxonomic range for this enzyme is: Aspergillus terreus

EC NUMBER
COMMENTARY hide
2.3.1.238
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RECOMMENDED NAME
GeneOntology No.
monacolin J acid methylbutanoate transferase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
monacolin J acid + (S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase] = lovastatin acid + [2-methylbutanoate polyketide synthase]
show the reaction diagram
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
lovastatin biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
monacolin J acid:(S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase] (S)-2-methylbutanoate transferase
The enzyme catalyses the ultimate reaction in the lovastatin biosynthesis pathway of the filamentous fungus Aspergillus terreus.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
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the enzyme is involved in lovastatin biosynthesis
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(S)-2-methylbutanoyl-N-acetylcysteamine + 6-hydroxy-6-demethylmonacolin J
pravastatin + N-acetylcysteamine
show the reaction diagram
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?
(S)-2-methylbutanoyl-N-acetylcysteamine + monacolin J
lovastatin + N-acetylcysteamine
show the reaction diagram
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-
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?
alpha-dimethylbutanoyl-N-acetylcysteamine + 6-hydroxy-6-demethylmonacolin J
huvastatin + N-acetylcysteamine
show the reaction diagram
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?
alpha-dimethylbutanoyl-N-acetylcysteamine + monacolin J
simvastatin + N-acetylcysteamine
show the reaction diagram
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-
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?
benzoyl-CoA + monacolin J
? + CoA
show the reaction diagram
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-
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?
butanoyl-N-acetylcysteamine + monacolin J
(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl butanoate + N-acetylcysteamine
show the reaction diagram
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?
butyryl-CoA + monacolin J
(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl butanoate + CoA
show the reaction diagram
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87% conversion after 10 h
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?
hexanoyl-N-acetylcysteamine + monacolin J
? + N-acetylcysteamine
show the reaction diagram
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?
monacolin J acid + (S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase]
lovastatin acid + [2-methylbutanoate polyketide synthase]
show the reaction diagram
pentanoyl-N-acetylcysteamine + monacolin J
? + N-acetylcysteamine
show the reaction diagram
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?
additional information
?
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the enzyme displays preference toward medium chain length (C3C6) acyl groups, with butyryl-CoA being the optimal alkylacyl-CoA substrate. Both acetyl- and octanoyl-CoA are poor substrates of LovD, with less than 10% acylation of monacolin J. The enzyme also catalyzes hydrolysis of lovastain to monacolin J. Butyryl-thioethane and butyryl-thioethanol are not competent substrates of the enzyme
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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
monacolin J acid + (S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase]
lovastatin acid + [2-methylbutanoate polyketide synthase]
show the reaction diagram
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
monacolin J
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competitive inhibitor of butyryl-CoA, substrate inhibition occurs due to binding of monacolin J to the free enzyme, forming a LovD-monacolin J complex and blocking entrance of butyryl-CoA
additional information
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no substrate inhibition by butyryl-CoA at high concentrations is observed
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.039
(S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase]
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pH and temperature not specified in the publication
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1.59
butyryl-CoA
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pH 7.9, 25C
additional information
additional information
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Km-value for hydrolysis of lovastain to monacolin J is 0.56 mM
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.806
(S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase]
Aspergillus terreus
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pH and temperature not specified in the publication
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additional information
additional information
Aspergillus terreus
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kcat-value for hydrolysis of lovastain to monacolin J is 0.0035/s
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
20.7
(S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase]
Aspergillus terreus
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pH and temperature not specified in the publication
196607
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.33
monacolin J
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pH 7.9, 25C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.9
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
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assay at
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
46000
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x * 46000, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 46000, SDS-PAGE
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
overexpression in Escherichia coli
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
synthesis
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the enzyme can be a useful biocatalyst for the synthesis of simvastatin and other statin analogs. It is an attractive enzyme for engineered biosynthesis of pharmaceutically important cholesterol-lowering drugs