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Information on EC 2.3.1.238 - monacolin J acid methylbutanoate transferase and Organism(s) Aspergillus terreus and UniProt Accession Q9Y7D1

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EC Tree
IUBMB Comments
The enzyme catalyses the ultimate reaction in the lovastatin biosynthesis pathway of the filamentous fungus Aspergillus terreus.
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This record set is specific for:
Aspergillus terreus
UNIPROT: Q9Y7D1
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The taxonomic range for the selected organisms is: Aspergillus terreus
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
+
(S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase]
=
+
[2-methylbutanoate polyketide synthase]
Synonyms
LovD, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
LovD
-
-
-
-
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.
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
-
-
-
?
(S)-2-methylbutanoyl-N-acetylcysteamine + monacolin J
lovastatin + N-acetylcysteamine
show the reaction diagram
-
-
-
?
alpha-dimethylbutanoyl-N-acetylcysteamine + 6-hydroxy-6-demethylmonacolin J
huvastatin + N-acetylcysteamine
show the reaction diagram
-
-
-
?
alpha-dimethylbutanoyl-N-acetylcysteamine + monacolin J
simvastatin + N-acetylcysteamine
show the reaction diagram
-
-
-
?
benzoyl-CoA + monacolin J
? + CoA
show the reaction diagram
-
-
-
?
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
-
-
-
?
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
87% conversion after 10 h
-
-
?
hexanoyl-N-acetylcysteamine + monacolin J
? + N-acetylcysteamine
show the reaction diagram
-
-
-
?
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
-
-
-
?
additional information
?
-
the enzyme displays preference toward medium chain length (C3–C6) 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
-
-
?
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
monacolin J acid + (S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase]
lovastatin acid + [2-methylbutanoate polyketide synthase]
show the reaction diagram
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
monacolin J
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
no substrate inhibition by butyryl-CoA at high concentrations is observed
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.039
(S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase]
pH and temperature not specified in the publication
-
1.59
butyryl-CoA
pH 7.9, 25°C
additional information
additional information
Km-value for hydrolysis of lovastain to monacolin J is 0.56 mM
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.806
(S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase]
pH and temperature not specified in the publication
-
additional information
additional information
kcat-value for hydrolysis of lovastain to monacolin J is 0.0035/s
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
20.7
(S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase]
pH and temperature not specified in the publication
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.33
monacolin J
pH 7.9, 25°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
the enzyme is involved in lovastatin biosynthesis
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
LOVD_ASPTE
413
0
46037
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
46000
x * 46000, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 46000, SDS-PAGE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overexpression in Escherichia coli
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
synthesis
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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kennedy, J.; Auclair, K.; Kendrew, S.G.; Park, C.; Vederas, J.C.; Hutchinson, C.R.
Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis
Science
284
1368-1372
1999
Aspergillus terreus (Q9Y7D1)
Manually annotated by BRENDA team
Xie, X.; Watanabe, K.; Wojcicki, W.A.; Wang, C.C.; Tang, Y.
Biosynthesis of lovastatin analogs with a broadly specific acyltransferase
Chem. Biol.
13
1161-1169
2006
Aspergillus terreus (Q9Y7D1)
Manually annotated by BRENDA team
Xie, X.; Meehan, M.J.; Xu, W.; Dorrestein, P.C.; Tang, Y.
Acyltransferase mediated polyketide release from a fungal megasynthase
J. Am. Chem. Soc.
131
8388-8389
2009
Aspergillus terreus (Q9Y7D1)
Manually annotated by BRENDA team