KEGG   ENZYME: 2.3.1.239Help
Entry
EC 2.3.1.239                Enzyme                                 

Name
10-deoxymethynolide synthase;
pikromycin PKS
Class
Transferases;
Acyltransferases;
Transferring groups other than aminoacyl groups
BRITE hierarchy
Sysname
(2S)-methylmalonyl-CoA:malonyl-CoA malonyltransferase (10-deoxymethynolide forming)
Reaction(IUBMB)
malonyl-CoA + 5 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+ = 10-deoxymethynolide + 6 CoA + 6 CO2 + 5 NADP+ + 2 H2O [RN:R06458]
Reaction(KEGG)
Substrate
malonyl-CoA [CPD:C00083];
(2S)-methylmalonyl-CoA [CPD:C00683];
NADPH [CPD:C00005];
H+ [CPD:C00080]
Product
10-deoxymethynolide [CPD:C11993];
CoA [CPD:C00010];
CO2 [CPD:C00011];
NADP+ [CPD:C00006];
H2O [CPD:C00001]
Comment
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.
History
EC 2.3.1.239 created 2014
Pathway
Biosynthesis of 12-, 14- and 16-membered macrolides
Biosynthesis of antibiotics
Orthology
K16000  
narbonolide/10-deoxymethynolide synthase
K16001  
narbonolide/10-deoxymethynolide synthase
K16002  
narbonolide/10-deoxymethynolide synthase
Reference
1  [PMID:12379101]
  Authors
Lu H, Tsai SC, Khosla C, Cane DE
  Title
Expression, site-directed mutagenesis, and steady state kinetic analysis of the terminal thioesterase domain of the methymycin/picromycin polyketide synthase.
  Journal
Biochemistry. 41 (2002) 12590-7.
Reference
2  [PMID:17719493]
  Authors
Kittendorf JD, Beck BJ, Buchholz TJ, Seufert W, Sherman DH
  Title
Interrogating the molecular basis for multiple macrolactone ring formation by the pikromycin polyketide synthase.
  Journal
Chem. Biol. 14 (2007) 944-54.
Reference
3  [PMID:19437523]
  Authors
Yan J, Gupta S, Sherman DH, Reynolds KA
  Title
Functional dissection of a multimodular polypeptide of the pikromycin polyketide  synthase into monomodules by using a matched pair of heterologous docking domains.
  Journal
Chembiochem. 10 (2009) 1537-43.
Reference
4  [PMID:24965656]
  Authors
Whicher JR, Dutta S, Hansen DA, Hale WA, Chemler JA, Dosey AM, Narayan AR, Hakansson K, Sherman DH, Smith JL, Skiniotis G
  Title
Structural rearrangements of a polyketide synthase module during its catalytic cycle.
  Journal
Nature. 510 (2014) 560-4.
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 

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