KEGG   ORTHOLOGY: K19886
Entry
K19886            Tight     KO                                     
Symbol
rebC
Name
flavin-dependent monooxygenase RebC [EC:1.13.12.17]
Pathway
map00404  Staurosporine biosynthesis
map01100  Metabolic pathways
map01110  Biosynthesis of secondary metabolites
Module
M00789  Rebeccamycin biosynthesis, tryptophan => rebeccamycin
Reaction
R09567  dichlorochromopyrrolate,NADH:oxygen 2,5-oxidoreductase (dichloroarcyriaflavin A-forming)
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
Other DBs
COG: COG0654
Genes
AG: BAC10676(rebC)
Reference
PMID:15743957
  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
[ag:BAC10676]
Reference
PMID:21290541
  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
LinkDB

KEGG   ORTHOLOGY: K19887
Entry
K19887            Tight     KO                                     
Symbol
rebP
Name
cytochrome P450 RebP [EC:1.13.12.17]
Pathway
map00404  Staurosporine biosynthesis
map01100  Metabolic pathways
map01110  Biosynthesis of secondary metabolites
Module
M00789  Rebeccamycin biosynthesis, tryptophan => rebeccamycin
Reaction
R09567  dichlorochromopyrrolate,NADH:oxygen 2,5-oxidoreductase (dichloroarcyriaflavin A-forming)
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
Other DBs
COG: COG2124
Genes
AG: BAC10677(rebP)
Reference
PMID:15743957
  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
[ag:BAC10677]
Reference
PMID:17705392
  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
LinkDB

KEGG   ENZYME: 1.13.12.17
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)
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)
R09567
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
ec01110  Biosynthesis of secondary metabolites
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
LinkDB

KEGG   REACTION: R09567
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
1.13.12.17
Pathway
rn00404  Staurosporine biosynthesis
rn01100  Metabolic pathways
rn01110  Biosynthesis of secondary metabolites
Module
M00789  Rebeccamycin biosynthesis, tryptophan => rebeccamycin
Brite
Enzymatic reactions [BR:br08201]
 1. Oxidoreductase reactions
  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
     R09567  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+
Orthology
K19886  flavin-dependent monooxygenase RebC [EC:1.13.12.17]
K19887  cytochrome P450 RebP [EC:1.13.12.17]
Other DBs
RHEA: 27317
LinkDB

DBGET integrated database retrieval system