KEGG   ORTHOLOGY: K16002
Entry
K16002            Tight     KO                                     
Symbol
pikAIII
Name
narbonolide/10-deoxymethynolide synthase [EC:2.3.1.240 2.3.1.239]
Pathway
map00522  Biosynthesis of 12-, 14- and 16-membered macrolides
map01052  Type I polyketide structures
map01100  Metabolic pathways
map01110  Biosynthesis of secondary metabolites
Module
M00776  Pikromycin/methymycin biosynthesis, methylmalonyl-CoA + malonyl-CoA => narbonolide/10-deoxymethynolide => pikromycin/methymycin
Reaction
R06458  (2S)-methylmalonyl-CoA:malonyl-CoA malonyltransferase (10-deoxymethynolide forming)
R06459  (2S)-methylmalonyl-CoA:malonyl-CoA malonyltransferase (narbonolide forming)
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   01052 Type I polyketide structures
    K16002  pikAIII; narbonolide/10-deoxymethynolide synthase
   00522 Biosynthesis of 12-, 14- and 16-membered macrolides
    K16002  pikAIII; narbonolide/10-deoxymethynolide synthase
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   01008 Polyketide biosynthesis proteins
    K16002  pikAIII; narbonolide/10-deoxymethynolide synthase
Enzymes [BR:ko01000]
 2. Transferases
  2.3  Acyltransferases
   2.3.1  Transferring groups other than aminoacyl groups
    2.3.1.239  10-deoxymethynolide synthase
     K16002  pikAIII; narbonolide/10-deoxymethynolide synthase
    2.3.1.240  narbonolide synthase
     K16002  pikAIII; narbonolide/10-deoxymethynolide synthase
Polyketide biosynthesis proteins [BR:ko01008]
 Polyketide synthase (PKS)
  Modular type I PKS
   cis-AT PKS
    Pikromycin PKS
     K16002  pikAIII; narbonolide/10-deoxymethynolide synthase
Genes
AG: AAC69331(pikAIII)
Reference
PMID:9770448
  Authors
Xue Y, Zhao L, Liu HW, Sherman DH
  Title
A gene cluster for macrolide antibiotic biosynthesis in Streptomyces venezuelae: architecture of metabolic diversity.
  Journal
Proc Natl Acad Sci U S A 95:12111-6 (1998)
DOI:10.1073/pnas.95.21.12111
  Sequence
[ag:AAC69331]
LinkDB

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
LinkDB

KEGG   REACTION: R06459
Entry
R06459                      Reaction                               
Name
(2S)-methylmalonyl-CoA:malonyl-CoA malonyltransferase (narbonolide forming)
Definition
6 (S)-Methylmalonyl-CoA + Malonyl-CoA + 5 NADPH + 5 H+ <=> Narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O
Equation
6 C00683 + C00083 + 5 C00005 + 5 C00080 <=> C11997 + 7 C00010 + 7 C00011 + 5 C00006 + 2 C00001
Comment
type I polyketide synthase, PikA1-4
Reaction class
RC00001  C00005_C00006
RC00004  C00010_C00083  C00010_C00683
RC02828  C00683_C11997
RC02829  C00683_C11997
RC02830  C00683_C11997
RC02910  C00683_C11997
RC02911  C00083_C11997
RC02915  C00683_C11997
RC03330  C00683_C11997
Enzyme
2.3.1.240
Pathway
rn00522  Biosynthesis of 12-, 14- and 16-membered macrolides
rn01100  Metabolic pathways
rn01110  Biosynthesis of secondary metabolites
Module
M00776  Pikromycin/methymycin biosynthesis, methylmalonyl-CoA + malonyl-CoA => narbonolide/10-deoxymethynolide => pikromycin/methymycin
Brite
Enzymatic reactions [BR:br08201]
 2. Transferase reactions
  2.3  Acyltransferases
   2.3.1  Transferring groups other than aminoacyl groups
    2.3.1.240
     R06459  6 (S)-Methylmalonyl-CoA + Malonyl-CoA + 5 NADPH + 5 H+ <=> Narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O
Orthology
K16000  narbonolide/10-deoxymethynolide synthase [EC:2.3.1.240 2.3.1.239]
K16001  narbonolide/10-deoxymethynolide synthase [EC:2.3.1.240 2.3.1.239]
K16002  narbonolide/10-deoxymethynolide synthase [EC:2.3.1.240 2.3.1.239]
K16003  narbonolide synthase [EC:2.3.1.240]
Other DBs
RHEA: 42847
LinkDB

DBGET integrated database retrieval system