KEGG   ORTHOLOGY: K16000
Entry
K16000            Tight     KO                                     
Symbol
pikAI
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
    K16000  pikAI; narbonolide/10-deoxymethynolide synthase
   00522 Biosynthesis of 12-, 14- and 16-membered macrolides
    K16000  pikAI; narbonolide/10-deoxymethynolide synthase
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   01008 Polyketide biosynthesis proteins
    K16000  pikAI; 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
     K16000  pikAI; narbonolide/10-deoxymethynolide synthase
    2.3.1.240  narbonolide synthase
     K16000  pikAI; narbonolide/10-deoxymethynolide synthase
Polyketide biosynthesis proteins [BR:ko01008]
 Polyketide synthase (PKS)
  Modular type I PKS
   cis-AT PKS
    Pikromycin PKS
     K16000  pikAI; narbonolide/10-deoxymethynolide synthase
Genes
AG: AAC69329(pikAI)
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:AAC69329]
LinkDB

KEGG   ENZYME: 2.3.1.239
Entry
EC 2.3.1.239                Enzyme                                 
Name
10-deoxymethynolide synthase;
pikromycin PKS
Class
Transferases;
Acyltransferases;
Transferring groups other than aminoacyl groups
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)
R06458
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
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
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]
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: 2.3.1.239
IUBMB Enzyme Nomenclature: 2.3.1.239
ExPASy - ENZYME nomenclature database: 2.3.1.239
BRENDA, the Enzyme Database: 2.3.1.239
LinkDB

KEGG   REACTION: R06458
Entry
R06458                      Reaction                               
Name
(2S)-methylmalonyl-CoA:malonyl-CoA malonyltransferase (10-deoxymethynolide forming)
Definition
5 (S)-Methylmalonyl-CoA + Malonyl-CoA + 5 NADPH + 5 H+ <=> 10-Deoxymethynolide + 6 CoA + 6 CO2 + 5 NADP+ + 2 H2O
Equation
5 C00683 + C00083 + 5 C00005 + 5 C00080 <=> C11993 + 6 C00010 + 6 C00011 + 5 C00006 + 2 C00001
Comment
type I polyketide synthase,PikA1-3
Reaction class
RC00001  C00005_C00006
RC00004  C00010_C00083  C00010_C00683
RC02829  C00683_C11993
RC02830  C00683_C11993
RC02831  C00683_C11993
RC02910  C00683_C11993
RC02911  C00083_C11993
RC02915  C00683_C11993
Enzyme
2.3.1.239
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
    2.3.1.239
     R06458  5 (S)-Methylmalonyl-CoA + Malonyl-CoA + 5 NADPH + 5 H+ <=> 10-Deoxymethynolide + 6 CoA + 6 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]
Other DBs
RHEA: 43059
LinkDB

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