KEGG   ENZYME: 2.3.1.240
Entry
EC 2.3.1.240                Enzyme                                 
Name
narbonolide synthase;
pikromycin PKS
Class
Transferases;
Acyltransferases;
Transferring groups other than aminoacyl groups
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)
R06459
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
ec01110  Biosynthesis of secondary metabolites
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
[ag:AAC69329 AAC69330 AAC69331 AAC69332]
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

  All links  
Pathway (7)   
   KEGG PATHWAY (6)   
   KEGG MODULE (1)   
Chemical substance (9)   
   KEGG COMPOUND (9)   
Chemical reaction (9)   
   KEGG REACTION (1)   
   KEGG RCLASS (8)   
Gene (8)   
   KEGG ORTHOLOGY (4)   
   KEGG GENES (4)   
Protein sequence (10)   
   UniProt (6)   
   SWISS-PROT (4)   
Protein domain (31)   
   InterPro (31)   
All databases (74)   

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