ID   REBD_LENAE              Reviewed;        1013 AA.
AC   Q8KHV6;
DT   16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   03-AUG-2022, entry version 54.
DE   RecName: Full=Dichlorochromopyrrolate synthase;
DE            EC=1.21.98.2 {ECO:0000269|PubMed:16313168};
DE   AltName: Full=Catalase;
DE            EC=1.11.1.6 {ECO:0000269|PubMed:16313168};
GN   Name=rebD; Synonyms=rbmC;
OS   Lentzea aerocolonigenes (Lechevalieria aerocolonigenes) (Saccharothrix
OS   aerocolonigenes).
OC   Bacteria; Actinobacteria; Pseudonocardiales; Pseudonocardiaceae; Lentzea.
OX   NCBI_TaxID=68170;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 39243 / DSM 44217 / BCRC 13729 / KCTC 9384;
RX   PubMed=11983340; DOI=10.1016/s1074-5521(02)00126-6;
RA   Sanchez C., Butovich I.A., Brana A.F., Rohr J., Mendez C., Salas J.A.;
RT   "The biosynthetic gene cluster for the antitumor rebeccamycin:
RT   characterization and generation of indolocarbazole derivatives.";
RL   Chem. Biol. 9:519-531(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=12617516; DOI=10.7164/antibiotics.55.1063;
RA   Onaka H., Taniguchi S., Igarashi Y., Furumai T.;
RT   "Cloning of the staurosporine biosynthetic gene cluster from Streptomyces
RT   sp. TP-A0274 and its heterologous expression in Streptomyces lividans.";
RL   J. Antibiot. 55:1063-1071(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Hyun C.-G., Bililign T., Liao J., Thorson J.S.;
RT   "The biosynthesis of indolocarbazoles in a heterologous E. coli host.";
RL   Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION IN THE REBECCAMYCIN
RP   BIOSYNTHESIS.
RC   STRAIN=ATCC 39243 / DSM 44217 / BCRC 13729 / KCTC 9384;
RX   PubMed=12619684; DOI=10.1271/bbb.67.127;
RA   Onaka H., Taniguchi S., Igarashi Y., Furumai T.;
RT   "Characterization of the biosynthetic gene cluster of rebeccamycin from
RT   Lechevalieria aerocolonigenes ATCC 39243.";
RL   Biosci. Biotechnol. Biochem. 67:127-138(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=14763561; DOI=10.7164/antibiotics.56.950;
RA   Onaka H., Taniguchi S., Ikeda H., Igarashi Y., Furumai T.;
RT   "pTOYAMAcos, pTYM18, and pTYM19, actinomycete-Escherichia coli integrating
RT   vectors for heterologous gene expression.";
RL   J. Antibiot. 56:950-956(2003).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=15743957; DOI=10.1128/jb.187.6.2084-2092.2005;
RA   Nishizawa T., Aldrich C.C., Sherman D.H.;
RT   "Molecular analysis of the rebeccamycin L-amino acid oxidase from
RT   Lechevalieria aerocolonigenes ATCC 39243.";
RL   J. Bacteriol. 187:2084-2092(2005).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Onaka H.;
RT   "Biosynthesis of heterocyclic antibiotics in actinomycetes and an approach
RT   to synthesize the natural compounds.";
RL   Nihon Hosenkin Gakkaishi 20:62-71(2006).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Asamizu S., Kato Y., Igarashi Y., Furumai T., Onaka H.;
RT   "Direct formation of chromopyrrolic acid from indole-3-pyruvic acid by
RT   StaD, a novel hemoprotein in indolocarbazole biosynthesis.";
RL   Tetrahedron Lett. 47:473-475(2006).
RN   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR,
RP   SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=ATCC 39243 / DSM 44217 / BCRC 13729 / KCTC 9384;
RX   PubMed=16313168; DOI=10.1021/bi051706e;
RA   Howard-Jones A.R., Walsh C.T.;
RT   "Enzymatic generation of the chromopyrrolic acid scaffold of rebeccamycin
RT   by the tandem action of RebO and RebD.";
RL   Biochemistry 44:15652-15663(2005).
RN   [10]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RC   STRAIN=ATCC 39243 / DSM 44217 / BCRC 13729 / KCTC 9384;
RX   PubMed=25837855; DOI=10.1016/j.abb.2015.03.020;
RA   Spolitak T., Ballou D.P.;
RT   "Evidence for catalytic intermediates involved in generating the
RT   chromopyrrolic acid scaffold of rebeccamycin by RebO and RebD.";
RL   Arch. Biochem. Biophys. 573:111-119(2015).
CC   -!- FUNCTION: Involved in the biosynthesis of the indolocarbazole antitumor
CC       agent rebeccamycin. Catalyzes the hydrogen peroxide-dependent
CC       dimerization of two L-tryptophan-derived molecules (imine form of
CC       indole 3-pyruvate (IPA)), to form dichlorochromopyrrolic acid (CPA),
CC       the precursor for the six-ring bisindolopyrrolocarbazole scaffold of
CC       the rebeccamycin. The hydrogen peroxide is provided together with
CC       iminoindolpropanoate by RebO. Due to the instability of indole 3-
CC       pyruvate (IPA), which is hydrolyzed in solution and exits in
CC       equilibrium with the predominant ketone form of IPA, the concerted
CC       functioning of the RebO/RebD system appears to prevent the buildup of
CC       significant amounts of IPA and its imine in solution, effectively
CC       shepherding the imine further down the biosynthetic chain.
CC       {ECO:0000269|PubMed:12619684, ECO:0000269|PubMed:16313168,
CC       ECO:0000269|PubMed:25837855}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 3-(7-chloroindol-3-yl)-2-iminopropanoate + H2O2 =
CC         dichlorochromopyrrolate + H(+) + 2 H2O + NH4(+);
CC         Xref=Rhea:RHEA:27393, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:59194,
CC         ChEBI:CHEBI:59198; EC=1.21.98.2;
CC         Evidence={ECO:0000269|PubMed:16313168, ECO:0000269|PubMed:25837855};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 2-iminio-3-(indol-3-yl)propanoate + H2O2 = chromopyrrolate +
CC         H(+) + 2 H2O + NH4(+); Xref=Rhea:RHEA:50920, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938,
CC         ChEBI:CHEBI:59193, ChEBI:CHEBI:133898; EC=1.21.98.2;
CC         Evidence={ECO:0000269|PubMed:25837855};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 H2O2 = 2 H2O + O2; Xref=Rhea:RHEA:20309, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:16240; EC=1.11.1.6;
CC         Evidence={ECO:0000269|PubMed:16313168};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000269|PubMed:16313168};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=150 mM for 2-imino-3-(indol-3-yl)propanoate (at pH 7.5)
CC         {ECO:0000269|PubMed:16313168};
CC         Note=kcat is 64000 min(-1) for 2-imino-3-(indol-3-yl)propanoate (at
CC         pH 7.5).;
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16313168}.
CC   -!- SIMILARITY: Belongs to the RebD family. {ECO:0000305}.
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DR   EMBL; AF534707; AAN01209.1; -; Genomic_DNA.
DR   EMBL; AB090952; BAC10675.1; -; Genomic_DNA.
DR   EMBL; AB071405; BAC15751.1; -; Genomic_DNA.
DR   EMBL; AJ414559; CAC93715.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q8KHV6; -.
DR   SMR; Q8KHV6; -.
DR   KEGG; ag:BAC10675; -.
DR   BioCyc; MetaCyc:MON-15087; -.
DR   BRENDA; 1.21.98.2; 4340.
DR   GO; GO:0004096; F:catalase activity; IEA:UniProtKB-EC.
DR   GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0046993; F:oxidoreductase activity, acting on X-H and Y-H to form an X-Y bond, with oxygen as acceptor; IDA:UniProtKB.
DR   Gene3D; 1.20.1260.10; -; 1.
DR   InterPro; IPR012347; Ferritin-like.
DR   InterPro; IPR026820; VioB/RebD_dom.
DR   Pfam; PF12902; Ferritin-like; 1.
PE   1: Evidence at protein level;
KW   Heme; Iron; Metal-binding; Oxidoreductase.
FT   CHAIN           1..1013
FT                   /note="Dichlorochromopyrrolate synthase"
FT                   /id="PRO_0000424087"
SQ   SEQUENCE   1013 AA;  110746 MW;  5CBC26E83DC67EC0 CRC64;
     MSVFDLPRLH FAGTATTRLP TGPRNGLVDL STHSVVMDGE RFPASRPAAE YHAYLDRVGG
     KGTAFAGNGY FAIDAGITAV ERAAGEVDTG DLLVGRAVDV WGHYNEYLAT TFNRARIFDV
     DPSSSWTSTV MIGQFGFGRL GRSHDVGYVF TGGVHGMQPP RWHEDGRVLH QFTVPAGEDM
     TWFGSAADSP AAARLRELVE SGEADGLVVQ LALSDAGPAP MPHAQQWRLR GTIAPWHAGE
     PRTCPAGRLL TPHNLTADLR GDHVSLNLIS FRPPTGISGL ELRTADTDRF IARVPADDPH
     GVVTVPAAEG GDEALCVVGT TAAGERIVVS REREVTVHVD DASVFLEHPR GPGDSDQDAE
     IAVRTYVRGE PAAATIHIGQ YFNPRAFPLD EHATAASATP EDLDVVALCV DGTRWSRHCV
     ISTDENGDGR FLLRGARPGA TRLLLSAEGA TPFDGLTAAA AYDNDDSLGL WSGLASVAVR
     VLPDHWWMDD IPRDKVTFDL LYREVFAFYE LLYSFMGEEV FSLADRFRVE THPRLIWQMC
     DPRNRAKTYY MPPTRDLTGP QARLLLAYLR AQNSDVVVPV IEPSHTRSGT PISTRTDLVR
     ALRHGVAIEL AVMLQYLYAA FSIPTHGAGQ ELVSRGDWTP EQLRLMCGDG GETTDGGVRG
     SLLGVAREEM IHFLVVNNVL MAVGEPFHVP DLDFGTINDT LMVPLDFSLE ALGLGSVQRF
     IQIEQPEGLT GAVRLGDLPV PVREAEDFHY ASLSELYGDI REGLQRVPGL FLVERGRGGG
     EHHLFLRESV NAVHPDYQLE VDDLSSALFA IDFVTEQGEG HVLTDEDTGE ESHYDTFVRV
     ADLLMKERLT AADTRRAQWS PAYPVARNPT VHGGGQSKEL VTSPVARELM VLFNKSYFMM
     LQLMVQHFGG SPDASLRRSK LMNAAIDVMT GVMRPLAELL VTVPSGRHGR TAGPSFELDE
     KPAFIPRADV ARRAISLRFR HLAESARTCA LVPDKVVRNL DFLADQFATE GPR