Information on EC 2.3.1.240 - narbonolide synthase

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The expected taxonomic range for this enzyme is: Streptomyces venezuelae

EC NUMBER
COMMENTARY hide
2.3.1.240
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RECOMMENDED NAME
GeneOntology No.
narbonolide synthase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+ = narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O
show the reaction diagram
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of 12-, 14- and 16-membered macrolides
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Biosynthesis of antibiotics
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narbomycin, pikromycin and novapikromycin biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
(2S)-methylmalonyl-CoA:malonyl-CoA malonyltransferase (narbonolide forming)
The product, narbonolide, contains a 14-membered ring and is an intermediate in the biosynthesis of narbonomycin and pikromycin in the bacterium Streptomyces venezuelae. 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.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1
the enzyme is involved in the biosynthesis of narbonomycin
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+
narbonolide + ?
show the reaction diagram
hexaketide N-acetyl cysteamine thioester + (2S)-methylmalonyl-CoA + NADPH + H+
narbonolide + ?
show the reaction diagram
malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+
narbonolide + 7 CoA + 7 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-dihydro-narbonolide + 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
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?
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 + 6 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+
narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O
show the reaction diagram
Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1
the product narbonolide 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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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.41
(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-valkue for activity with the polyketide synthase PikAIII/polyketide synthase PikAIV complex in formation of narbonolide
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additional information
additional information
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.055
(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 narbonolide
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additional information
additional information
Streptomyces venezuelae
Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1
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
0.13
(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 narbonolide
197629
additional information
additional information
Streptomyces venezuelae
Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1
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
Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1
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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overexpression of polyketide synthase PikAIII, and polyketide synthase 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
Q9ZGI5 and Q9ZGI4 and Q9ZGI3 and Q9ZGI2 and Q9ZGI1
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
synthesis