2.3.1.240: narbonolide synthase
This is an abbreviated version!
For detailed information about narbonolide synthase, go to the full flat file.
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
2.3.1.240 narbonolide synthaseAdvanced search results
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results (Substrates Products
Substrates Products on EC 2.3.1.240 - narbonolide 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+
narbonolide + ?
hexaketide N-acetyl cysteamine thioester + (2S)-methylmalonyl-CoA + NADPH + H+
narbonolide + ?
malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+
narbonolide + 7 CoA + 7 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-dihydro-narbonolide + 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
?
-
-
-
-
?
(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+
narbonolide + ?
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+
narbonolide + ?
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
-
-
?
hexaketide N-acetyl cysteamine thioester + (2S)-methylmalonyl-CoA + NADPH + H+
narbonolide + ?
incubation of the monomodular polyketide synthase PikAIV with hexaketide and 2-methylmalonyl-CoA results in chain extension to the final heptaketide, release, and cyclization to afford narbonolide. The polyketide synthase PikAIII/polyketide synthase PikAIV complex processes the pentaketide to produce 10-deoxymethynolide and narbonolide. No activity with (E)-(2S,4R,8R,9R)-S-2-acetamidoethyl 9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate (i.e. pentaketide) to produce 10-deoxymethynolide
-
-
?
hexaketide N-acetyl cysteamine thioester + (2S)-methylmalonyl-CoA + NADPH + H+
narbonolide + ?
incubation of the monomodular polyketide synthase PikAIV with hexaketide and 2-methylmalonyl-CoA results in chain extension to the final heptaketide, release, and cyclization to afford narbonolide. The polyketide synthase PikAIII/polyketide synthase PikAIV complex processes the pentaketide to produce 10-deoxymethynolide and narbonolide. No activity with (E)-(2S,4R,8R,9R)-S-2-acetamidoethyl 9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate (i.e. pentaketide) to produce 10-deoxymethynolide
-
-
?
malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+
narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O
the product narbonolide is an intermediate in the biosynthesis of methymycin
-
-
?
malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+
narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O
the enzyme also produces 10-deoxymethynolide (see EC 2.3.1.239, 10-deoxymethynolide 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-dihydro-narbonolide + 10-deoxymethynolide + CoA + CO2 + NADP+ + H2O
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-
products formed by chimeric polykeitde synthase construcuts
-
?
methylmalonyl-N-acetylcysteamine + S-phenyl (2S,4R,6E,8R,9R)-9-hydroxy-2,4,8-trimethyl-5-oxoundec-6-enethioate
3-dihydro-narbonolide + 10-deoxymethynolide + CoA + CO2 + NADP+ + H2O
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products formed by chimeric polykeitde synthase construcuts
-
?
additional information
?
-
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
?
-
-
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
-
-
?
additional information
?
-
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
-
-
?
