Information on EC 2.3.1.239 - 10-deoxymethynolide synthase

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The expected taxonomic range for this enzyme is: Streptomyces venezuelae

EC NUMBER
COMMENTARY hide
2.3.1.239
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RECOMMENDED NAME
GeneOntology No.
10-deoxymethynolide synthase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
malonyl-CoA + 5 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+ = 10-deoxymethynolide + 6 CoA + 6 CO2 + 5 NADP+ + 2 H2O
show the reaction diagram
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
methymycin, neomethymycin and novamethymycin biosynthesis
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Biosynthesis of 12-, 14- and 16-membered macrolides
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Biosynthesis of antibiotics
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SYSTEMATIC NAME
IUBMB Comments
(2S)-methylmalonyl-CoA:malonyl-CoA malonyltransferase (10-deoxymethynolide forming)
The product, 10-deoxymethynolide, contains a 12-membered ring and is an intermediate in the biosynthesis of methymycin in the bacterium Streptomyces venezuelae. The enzyme also produces narbonolide (see EC 2.3.1.240, narbonolide synthase). The enzyme has 29 active sites arranged in four polypeptides (pikAI - pikAIV) with a loading domain, six extension modules and a terminal thioesterase domain. Each extension module contains a ketosynthase (KS), keto reductase (KR), an acyltransferase (AT) and an acyl-carrier protein (ACP). Not all active sites are used in the biosynthesis.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
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the enzyme is involved in the biosynthesis of methymycin
physiological function
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in modular type I polyketide synthases the presence of the three processing domains, i.e. ketoreductase (KR), dehydratase (DH), and enoylreductase (ER), are varied in each module, leading to a fully reduced, partially reduced, or unreduced segment on the polyketide chain. Dehydratase PikDH2 converts D-alcohol substrates to trans-olefin products. The reaction is reversible with equilibrium constants ranging from 1.2 to 2. The enzyme activity is robust, and PikDH2 can be used for the chemoenzymatic synthesis of unsaturated triketide products. PikDH2 shows remarkably strict substrate specificity and is unable to turn over substrates that are epimeric at the beta-, gamma-, or delta-position
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(3R,4R,5E,8R,10S,11S,12R)-3-hydroxy-4,8,10,12-tetramethyl-11-[[(2-nitrophenyl)methoxy]methoxy]-13-(phenylsulfanyl)tridec-5-en-7-one + methylmalonyl N-acetylcysteamine
?
show the reaction diagram
(E)-(2S,4R,8R,9R)-S-2-acetamidoethyl 9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate + (2S)-methylmalonyl-CoA + NADPH + H+
10-deoxymethynolide + ?
show the reaction diagram
malonyl-CoA + 5 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+
10-deoxymethynolide + 6 CoA + 6 CO2 + 5 NADP+ + 2 H2O
show the reaction diagram
methylmalonyl-N-acetylcysteamine + S-phenyl (2S,4R,6E,8R,9R)-9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate
3-dehydro-10-deoxymethynolide + 10-deoxymethynolide + CoA + CO2 + NADP+ + H2O
show the reaction diagram
N-(2-[[(2R,3S,4S,6R,8E,10R,11R)-11-hydroxy-2,4,6,10-tetramethyl-3-[[(2-nitrophenyl)methoxy]methoxy]-7-oxotridec-8-en-1-yl]sulfanyl]ethyl)acetamide + methylmalonyl N-acetylcysteamine
?
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
malonyl-CoA + 5 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+
10-deoxymethynolide + 6 CoA + 6 CO2 + 5 NADP+ + 2 H2O
show the reaction diagram
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the product 10-deoxymethynolide is an intermediate in the biosynthesis of methymycin
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?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
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enzyme utilizes an oxidized quinone as co-factor
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.25
(E)-(2S,4R,8R,9R)-S-2-acetamidoethyl 9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate
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pH 7.2, 30C, KM-value for activity with the polyketide synthase PikAIII/polyketide synthase PikAIV complex in formation of 10-deoxymethynolide
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additional information
additional information
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.05
(E)-(2S,4R,8R,9R)-S-2-acetamidoethyl 9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate
Streptomyces venezuelae
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pH 7.2, 30C, kcat for activity with the polyketide synthase PikAIII/polyketide synthase PikAIV complex in formation of 10-deoxymethynolide
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additional information
additional information
Streptomyces venezuelae
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steady state kinetic parameters for diketides with wild-type and mutant thioesterase domain of methymycin/picromycin synthase
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.2
(E)-(2S,4R,8R,9R)-S-2-acetamidoethyl 9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate
Streptomyces venezuelae
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pH 7.2, 30C, kcat/Km-value for activity with the polyketide synthase PikAIII/polyketide synthase PikAIV complex in formation of 10-deoxymethynolide
197629
additional information
additional information
Streptomyces venezuelae
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steady state kinetic parameters for diketides with wild-type and mutant thioesterase domain of methymycin/picromycin synthase
2
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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pH-dependence of the hydrolysis of thioesters by the thioesterase domain of methymycin/picromycin synthase with diketides
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
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expression in Streptomyces venezuelae
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expression of functional polyketide synthase modules in Escherichia coli
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overexpression of pikromycin modules PikAIII and PIkAIV in Escherichia coli
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the picromycin/methymycin PKS genes (pikAI, PikAII, PikAIII, PikAIV and pikAV) are functionally expressed in the heterologous host Streptomyces lividans, resulting in production of both narbonolide and 10-deoxymethynolide
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the thioesterase domain of the methymycin/picromycin synthase (PICS) is functionally expressed in Escherichia coli
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
synthesis