KEGG   ENZYME: 2.3.1.240Help
Entry
EC 2.3.1.240                Enzyme                                 

Name
narbonolide synthase;
pikromycin PKS
Class
Transferases;
Acyltransferases;
Transferring groups other than aminoacyl groups
BRITE hierarchy
Sysname
(2S)-methylmalonyl-CoA:malonyl-CoA malonyltransferase (narbonolide forming)
Reaction(IUBMB)
malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH + 5 H+ = narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O [RN:R06459]
Reaction(KEGG)
Substrate
malonyl-CoA [CPD:C00083];
(2S)-methylmalonyl-CoA [CPD:C00683];
NADPH [CPD:C00005];
H+ [CPD:C00080]
Product
narbonolide [CPD:C11997];
CoA [CPD:C00010];
CO2 [CPD:C00011];
NADP+ [CPD:C00006];
H2O [CPD:C00001]
Comment
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.
History
EC 2.3.1.240 created 2014
Pathway
ec00522  Biosynthesis of 12-, 14- and 16-membered macrolides
ec01100  Metabolic pathways
ec01130  Biosynthesis of antibiotics
Orthology
K16000  narbonolide/10-deoxymethynolide synthase
K16001  narbonolide/10-deoxymethynolide synthase
K16002  narbonolide/10-deoxymethynolide synthase
K16003  narbonolide 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 41:12590-7 (2002)
DOI:10.1021/bi026006d
  Sequence
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 14:944-54 (2007)
DOI:10.1016/j.chembiol.2007.07.013
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 10:1537-43 (2009)
DOI:10.1002/cbic.200900098
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 510:560-4 (2014)
DOI:10.1038/nature13409
Other DBs
ExplorEnz - The Enzyme Database: 2.3.1.240
IUBMB Enzyme Nomenclature: 2.3.1.240
ExPASy - ENZYME nomenclature database: 2.3.1.240
BRENDA, the Enzyme Database: 2.3.1.240

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