2.3.1.239: 10-deoxymethynolide synthase
This is an abbreviated version!
For detailed information about 10-deoxymethynolide synthase, go to the full flat file.
Word Map on EC 2.3.1.239
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2.3.1.239
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venezuelae
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macrolactone
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14-membered
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thioesterase
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narbonolide
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macrolide
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synthases
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6-deoxyerythronolide
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cyclization
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triketide
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hexaketide
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erythromycin
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n-acetylcysteamine
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macrocyclization
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te
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ketosynthase
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ketoreductase
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plasmid-based
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synthesis
- 2.3.1.239
- venezuelae
-
macrolactone
-
14-membered
-
thioesterase
- narbonolide
-
macrolide
- synthases
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6-deoxyerythronolide
-
cyclization
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triketide
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hexaketide
- erythromycin
- n-acetylcysteamine
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macrocyclization
- te
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ketosynthase
- ketoreductase
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plasmid-based
- synthesis
Reaction
Synonyms
methymycin/picromycin polyketide synthase, picromycin/methymycin PKS, picromycin/methymycin polyketide synthase, PICS, PikAI, PikAIII, PikAIV, pikromycin PKS, pikromycin polyketide synthase, type I polyketide synthase PikAIV
ECTree
2.3.1.239 10-deoxymethynolide synthaseAdvanced search results
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results (Substrates Products
Substrates Products on EC 2.3.1.239 - 10-deoxymethynolide synthase
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SUBSTRATE 
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
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
?
(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 + ?
malonyl-CoA + 5 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+
10-deoxymethynolide + 6 CoA + 6 CO2 + 5 NADP+ + 2 H2O
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
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
?
(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
?
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-
-
-
?
(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
?
-
-
-
-
?
(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 + ?
pikromycin modules PikAIII and PikAIV generate the 12-membered ring macrocycle most efficiently when engaged in their native protein-protein interaction. PikAIV adopts an alternative conformation that enables the terminal thioesterase domain to directly off-load the PikAIII-bound hexaketide intermediate for macrocyclization
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-
?
(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 + ?
the engineered polyketide synthase PikAIII-TE(thioesterase domain) fusion protein accepts and processes the pentaketide to produce 10-deoxymethynolide as the sole product. The polyketide synthase PikAIII/polyketide synthase PikAIV complex processes the pentaketide to produce 10-deoxymethynolide and narbonolide. After incubation of the hexaketide with polyketide synthase PikAIII-TE(thioesterase domain) fusion protein in both the presence and absence of NADPH, no product formation is observed
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-
?
(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 + ?
-
the engineered polyketide synthase PikAIII-TE(thioesterase domain) fusion protein accepts and processes the pentaketide to produce 10-deoxymethynolide as the sole product. The polyketide synthase PikAIII/polyketide synthase PikAIV complex processes the pentaketide to produce 10-deoxymethynolide and narbonolide. After incubation of the hexaketide with polyketide synthase PikAIII-TE(thioesterase domain) fusion protein in both the presence and absence of NADPH, no product formation is observed
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-
?
malonyl-CoA + 5 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+
10-deoxymethynolide + 6 CoA + 6 CO2 + 5 NADP+ + 2 H2O
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the product 10-deoxymethynolide is an intermediate in the biosynthesis of methymycin
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-
?
malonyl-CoA + 5 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+
10-deoxymethynolide + 6 CoA + 6 CO2 + 5 NADP+ + 2 H2O
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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
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-
?
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
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products formed by chimeric polyketide synthase construcuts
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?
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
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products formed by chimeric polyketide synthase construcuts
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?
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
?
-
-
-
-
?
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
?
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?
additional information
?
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despite clear similarities in biochemistry and underlying module organization the picromycin synthase modules 5+TE(thioesterase) and 6+TE(thioesterase) show clear differences in substrate specificity and tolerance
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?
additional information
?
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by modification of the type of hexaketide ester employed, product formation may be controled with greater than 10:1 selectivity for either full module catalysis, leading to a 14-membered macrolactone, or direct cyclization to a 12-membered ring
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-
?
additional information
?
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by modification of the type of hexaketide ester employed, product formation may be controled with greater than 10:1 selectivity for either full module catalysis, leading to a 14-membered macrolactone, or direct cyclization to a 12-membered ring
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-
?
additional information
?
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despite clear similarities in biochemistry and underlying module organization the picromycin synthase modules 5+TE(thioesterase) and 6+TE(thioesterase) show clear differences in substrate specificity and tolerance
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-
?
