KEGG   ORTHOLOGY: K19886Help
Entry
K19886                      KO                                     

Name
rebC
Definition
flavin-dependent monooxygenase RebC [EC:1.13.12.17]
Pathway
ko00404  Staurosporine biosynthesis
ko01100  Metabolic pathways
ko01130  Biosynthesis of antibiotics
Module
M00789  Rebeccamycin biosynthesis, tryptophan => rebeccamycin
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09110 Biosynthesis of other secondary metabolites
   00404 Staurosporine biosynthesis
    K19886  rebC; flavin-dependent monooxygenase RebC
Enzymes [BR:ko01000]
 1. Oxidoreductases
  1.13  Acting on single donors with incorporation of molecular oxygen (oxygenases)
   1.13.12  With incorporation of one atom of oxygen (internal monooxygenases or internal mixed-function oxidases)
    1.13.12.17  dichloroarcyriaflavin A synthase
     K19886  rebC; flavin-dependent monooxygenase RebC
BRITE hierarchy
Other DBs
RN: R09567
COG: COG0654
Genes
AG: BAC10676(rebC)
TaxonomyKoalaUniProt
Reference
  Authors
Nishizawa T, Aldrich CC, Sherman DH
  Title
Molecular analysis of the rebeccamycin L-amino acid oxidase from Lechevalieria aerocolonigenes ATCC 39243.
  Journal
J Bacteriol 187:2084-92 (2005)
DOI:10.1128/JB.187.6.2084-2092.2005
  Sequence
Reference
  Authors
Groom K, Bhattacharya A, Zechel DL
  Title
Rebeccamycin and staurosporine biosynthesis: insight into the mechanisms of the flavin-dependent monooxygenases RebC and StaC.
  Journal
Chembiochem 12:396-400 (2011)
DOI:10.1002/cbic.201000580

KEGG   ORTHOLOGY: K19887Help
Entry
K19887                      KO                                     

Name
rebP
Definition
cytochrome P450 RebP [EC:1.13.12.17]
Pathway
ko00404  Staurosporine biosynthesis
ko01100  Metabolic pathways
ko01130  Biosynthesis of antibiotics
Module
M00789  Rebeccamycin biosynthesis, tryptophan => rebeccamycin
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09110 Biosynthesis of other secondary metabolites
   00404 Staurosporine biosynthesis
    K19887  rebP; cytochrome P450 RebP
Enzymes [BR:ko01000]
 1. Oxidoreductases
  1.13  Acting on single donors with incorporation of molecular oxygen (oxygenases)
   1.13.12  With incorporation of one atom of oxygen (internal monooxygenases or internal mixed-function oxidases)
    1.13.12.17  dichloroarcyriaflavin A synthase
     K19887  rebP; cytochrome P450 RebP
BRITE hierarchy
Other DBs
RN: R09567
COG: COG2124
Genes
AG: BAC10677(rebP)
TaxonomyKoalaUniProt
Reference
  Authors
Nishizawa T, Aldrich CC, Sherman DH
  Title
Molecular analysis of the rebeccamycin L-amino acid oxidase from Lechevalieria aerocolonigenes ATCC 39243.
  Journal
J Bacteriol 187:2084-92 (2005)
DOI:10.1128/JB.187.6.2084-2092.2005
  Sequence
Reference
  Authors
Howard-Jones AR, Walsh CT
  Title
Nonenzymatic oxidative steps accompanying action of the cytochrome P450 enzymes StaP and RebP in the biosynthesis of staurosporine and rebeccamycin.
  Journal
J Am Chem Soc 129:11016-7 (2007)
DOI:10.1021/ja0743801

KEGG   ENZYME: 1.13.12.17Help
Entry
EC 1.13.12.17               Enzyme                                 

Name
dichloroarcyriaflavin A synthase
Class
Oxidoreductases;
Acting on single donors with incorporation of molecular oxygen (oxygenases);
With incorporation of one atom of oxygen (internal monooxygenases or internal mixed-function oxidases)
BRITE hierarchy
Sysname
dichlorochromopyrrolate,NADH:oxygen 2,5-oxidoreductase (dichloroarcyriaflavin A-forming)
Reaction(IUBMB)
dichlorochromopyrrolate + 4 O2 + 4 NADH + 4 H+ = dichloroarcyriaflavin A + 2 CO2 + 6 H2O + 4 NAD+ [RN:R09567]
Reaction(KEGG)
Substrate
dichlorochromopyrrolate [CPD:C19698];
O2 [CPD:C00007];
NADH [CPD:C00004];
H+ [CPD:C00080]
Product
dichloroarcyriaflavin A [CPD:C19699];
CO2 [CPD:C00011];
H2O [CPD:C00001];
NAD+ [CPD:C00003]
Comment
The conversion of dichlorochromopyrrolate to dichloroarcyriaflavin A is a complex process that involves two enzyme components. RebP is an NAD-dependent cytochrome P-450 oxygenase that performs an aryl-aryl bond formation yielding the six-ring indolocarbazole scaffold [1]. Along with RebC, a flavin-dependent hydroxylase, it also catalyses the oxidative decarboxylation of both carboxyl groups. The presence of RebC ensures that the only product is the rebeccamycin aglycone dichloroarcyriaflavin A [2]. The enzymes are similar, but not identical, to StaP and StaC, which are involved in the synthesis of staurosporine [3].
History
EC 1.13.12.17 created 2010
Pathway
ec00404  Staurosporine biosynthesis
ec01100  Metabolic pathways
ec01130  Biosynthesis of antibiotics
Orthology
K19886  flavin-dependent monooxygenase RebC
K19887  cytochrome P450 RebP
Reference
1  [PMID:17606921]
  Authors
Makino M, Sugimoto H, Shiro Y, Asamizu S, Onaka H, Nagano S
  Title
Crystal structures and catalytic mechanism of cytochrome P450 StaP that produces  the indolocarbazole skeleton.
  Journal
Proc Natl Acad Sci U S A 104:11591-6 (2007)
DOI:10.1073/pnas.0702946104
Reference
2  [PMID:16967980]
  Authors
Howard-Jones AR, Walsh CT
  Title
Staurosporine and rebeccamycin aglycones are assembled by the oxidative action of StaP, StaC, and RebC on chromopyrrolic acid.
  Journal
J Am Chem Soc 128:12289-98 (2006)
DOI:10.1021/ja063898m
Reference
3  [PMID:15625109]
  Authors
Sanchez C, Zhu L, Brana AF, Salas AP, Rohr J, Mendez C, Salas JA
  Title
Combinatorial biosynthesis of antitumor indolocarbazole compounds.
  Journal
Proc Natl Acad Sci U S A 102:461-6 (2005)
DOI:10.1073/pnas.0407809102
Other DBs
ExplorEnz - The Enzyme Database: 1.13.12.17
IUBMB Enzyme Nomenclature: 1.13.12.17
ExPASy - ENZYME nomenclature database: 1.13.12.17
BRENDA, the Enzyme Database: 1.13.12.17

KEGG   REACTION: R09567Help
Entry
R09567                      Reaction                               

Name
dichlorochromopyrrolate,NADH:oxygen 2,5-oxidoreductase (dichloroarcyriaflavin A-forming)
Definition
3,4-Bis(7-chloroindol-3-yl)pyrrole-2,5-dicarboxylate + 4 Oxygen + 4 NADH + 4 H+ <=> Dichloroarcyriaflavin A + 2 CO2 + 6 H2O + 4 NAD+
Equation
C19698 + 4 C00007 + 4 C00004 + 4 C00080 <=> C19699 + 2 C00011 + 6 C00001 + 4 C00003
Reaction class
RC00001  C00003_C00004
RC02569  C19698_C19699
Enzyme
Pathway
rn00404  Staurosporine biosynthesis
rn01100  Metabolic pathways
rn01130  Biosynthesis of antibiotics
Module
M00789  Rebeccamycin biosynthesis, tryptophan => rebeccamycin
Orthology
K19886  flavin-dependent monooxygenase RebC [EC:1.13.12.17]
K19887  cytochrome P450 RebP [EC:1.13.12.17]
Other DBs
RHEA: 27317

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