ID OTAC_ASPNC Reviewed; 509 AA.
AC A2R6G9;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 27-MAR-2024, entry version 82.
DE RecName: Full=Cytochrome P450 monooxygenase otaC {ECO:0000303|PubMed:27667988};
DE EC=1.14.14.- {ECO:0000305|PubMed:27667988};
DE AltName: Full=Ochratoxin biosynthesis cluster protein 3 {ECO:0000303|PubMed:27667988};
DE AltName: Full=Ochratoxin biosynthesis cluster protein C {ECO:0000303|PubMed:33391201};
GN Name=otaC {ECO:0000303|PubMed:33391201};
GN Synonyms=ota3 {ECO:0000303|PubMed:27667988}; ORFNames=An15g07900;
OS Aspergillus niger (strain ATCC MYA-4892 / CBS 513.88 / FGSC A1513).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=425011;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4892 / CBS 513.88 / FGSC A1513;
RX PubMed=17259976; DOI=10.1038/nbt1282;
RA Pel H.J., de Winde J.H., Archer D.B., Dyer P.S., Hofmann G., Schaap P.J.,
RA Turner G., de Vries R.P., Albang R., Albermann K., Andersen M.R.,
RA Bendtsen J.D., Benen J.A.E., van den Berg M., Breestraat S., Caddick M.X.,
RA Contreras R., Cornell M., Coutinho P.M., Danchin E.G.J., Debets A.J.M.,
RA Dekker P., van Dijck P.W.M., van Dijk A., Dijkhuizen L., Driessen A.J.M.,
RA d'Enfert C., Geysens S., Goosen C., Groot G.S.P., de Groot P.W.J.,
RA Guillemette T., Henrissat B., Herweijer M., van den Hombergh J.P.T.W.,
RA van den Hondel C.A.M.J.J., van der Heijden R.T.J.M., van der Kaaij R.M.,
RA Klis F.M., Kools H.J., Kubicek C.P., van Kuyk P.A., Lauber J., Lu X.,
RA van der Maarel M.J.E.C., Meulenberg R., Menke H., Mortimer M.A.,
RA Nielsen J., Oliver S.G., Olsthoorn M., Pal K., van Peij N.N.M.E.,
RA Ram A.F.J., Rinas U., Roubos J.A., Sagt C.M.J., Schmoll M., Sun J.,
RA Ussery D., Varga J., Vervecken W., van de Vondervoort P.J.J., Wedler H.,
RA Woesten H.A.B., Zeng A.-P., van Ooyen A.J.J., Visser J., Stam H.;
RT "Genome sequencing and analysis of the versatile cell factory Aspergillus
RT niger CBS 513.88.";
RL Nat. Biotechnol. 25:221-231(2007).
RN [2]
RP IDENTIFICATION.
RX PubMed=22341916; DOI=10.1016/j.ijfoodmicro.2012.01.020;
RA Ferracin L.M., Fier C.B., Vieira M.L., Monteiro-Vitorello C.B.,
RA Varani A.M., Rossi M.M., Mueller-Santos M., Taniwaki M.H.,
RA Thie Iamanaka B., Fungaro M.H.;
RT "Strain-specific polyketide synthase genes of Aspergillus niger.";
RL Int. J. Food Microbiol. 155:137-145(2012).
RN [3]
RP FUNCTION.
RX PubMed=27667988; DOI=10.3389/fmicb.2016.01412;
RA Susca A., Proctor R.H., Morelli M., Haidukowski M., Gallo A.,
RA Logrieco A.F., Moretti A.;
RT "Variation in fumonisin and ochratoxin production associated with
RT differences in biosynthetic gene content in Aspergillus niger and A.
RT welwitschiae isolates from multiple crop and geographic origins.";
RL Front. Microbiol. 7:1412-1412(2016).
RN [4]
RP NOMENCLATURE, AND FUNCTION.
RX PubMed=33391201; DOI=10.3389/fmicb.2020.581309;
RA Ferrara M., Gallo A., Perrone G., Magista D., Baker S.E.;
RT "Comparative genomic analysis of ochratoxin A biosynthetic cluster in
RT producing fungi: new evidence of a cyclase gene involvement.";
RL Front. Microbiol. 11:581309-581309(2020).
RN [5]
RP INDUCTION.
RX PubMed=35143724; DOI=10.1021/acs.jafc.1c08160;
RA Zhang J., Li L., Yang Y., Zhao C., Hu J., Xue X., Gao Q., Wang D.,
RA Zhuang Z., Zhang Y.;
RT "Deletion and overexpression of the AnOTAbzip gene, a positive regulator of
RT ochratoxin A biosynthesis in Aspergillus niger.";
RL J. Agric. Food Chem. 70:2169-2178(2022).
RN [6]
RP INDUCTION.
RX PubMed=36006213; DOI=10.3390/toxins14080551;
RA Wei S., Hu C., Nie P., Zhai H., Zhang S., Li N., Lv Y., Hu Y.;
RT "Insights into the Underlying Mechanism of Ochratoxin A Production in
RT Aspergillus niger CBS 513.88 Using Different Carbon Sources.";
RL Toxins 14:551-551(2022).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of ochratoxin A (OTA), a mycotoxin composed
CC of a chlorinated type I polyketide dihydroisocoumarin moiety linked to
CC L-phenylalanine, and demonstrated to have nephrotoxic, immunotoxic,
CC genotoxic, neurotoxic, and teratogenic properties (PubMed:27667988).
CC OtaC catalyzes the oxidation of 7-methylmellein (7-MM) into 7-
CC carboxymellein (By similarity). The pathway begins with the highly
CC reducing polyketide synthase otaA that catalyzes the formation of the
CC isocoumarin group during the initial stages of biosynthesis, starting
CC from one acetate and 4 malonate units, to originate the characteristic
CC pentaketide skeleton 7-methylmellein (7-MM) of the OTA molecule. The
CC newly identified cyclase otaY might be involved in the polyketide
CC cyclization reaction during the initial steps of the OTA biosynthesis.
CC 7-MM is then oxidized into 7-carboxymellein (also called ochratoxin
CC beta) by the cytochrome P450 monooxygenase otaC. The NRPS encoded by
CC the otaB gene is involved in the linking of phenylalanine to the
CC dihydroisocoumarin ring. The reaction catalyzed by NRPS results in the
CC production of ochratoxin B (OTB), which is the non-chlorinated analog
CC of OTA and which subsequently serves as the substrate of the halogenase
CC otaD for chlorination activity to form the final molecular structure of
CC OTA, containing a chlorine atom in the C-5 position of the molecule
CC (PubMed:27667988, PubMed:33391201) (Probable).
CC {ECO:0000250|UniProtKB:A0A1R3RGJ7, ECO:0000269|PubMed:27667988,
CC ECO:0000305|PubMed:27667988, ECO:0000305|PubMed:33391201}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-methylmellein + 3 O2 + 3 reduced [NADPH--hemoprotein
CC reductase] = 7-carboxymellein + 4 H(+) + 4 H2O + 3 oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:72771, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:192524, ChEBI:CHEBI:192525;
CC Evidence={ECO:0000305|PubMed:27667988};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:72772;
CC Evidence={ECO:0000305|PubMed:27667988};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000250|UniProtKB:A0A1R3RGJ7}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is positively regulated by the ochratoxin cluster
CC transcription factor otaR1, probably via its binding to the conserved
CC 5'-ACGT-3' bZIP binding motifs found in multiple copies (3 to 4) in the
CC promoters of the OTA biosynthetic genes (PubMed:35143724). Expression
CC is induced by sucrose, glucose and arabinose which repress the gal4
CC transcription factor, a negative regulator of the ochratoxin gene
CC cluster (PubMed:36006213). {ECO:0000269|PubMed:35143724,
CC ECO:0000269|PubMed:36006213}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AM270352; CAK42677.1; -; Genomic_DNA.
DR RefSeq; XP_001397311.1; XM_001397274.1.
DR AlphaFoldDB; A2R6G9; -.
DR SMR; A2R6G9; -.
DR GlyCosmos; A2R6G9; 2 sites, No reported glycans.
DR EnsemblFungi; CAK42677; CAK42677; An15g07900.
DR GeneID; 4988391; -.
DR KEGG; ang:An15g07900; -.
DR VEuPathDB; FungiDB:An15g07900; -.
DR HOGENOM; CLU_001570_14_4_1; -.
DR OrthoDB; 3184603at2759; -.
DR Proteomes; UP000006706; Chromosome 3R.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; TAS:UniProt.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:1900818; P:ochratoxin A biosynthetic process; ISS:GO_Central.
DR CDD; cd11062; CYP58-like; 1.
DR Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR PANTHER; PTHR24305; CYTOCHROME P450; 1.
DR PANTHER; PTHR24305:SF242; CYTOCHROME P450 MONOOXYGENASE ATNE-RELATED; 1.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; Cytochrome P450; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 2: Evidence at transcript level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..509
FT /note="Cytochrome P450 monooxygenase otaC"
FT /evidence="ECO:0000255"
FT /id="PRO_0000440591"
FT TRANSMEM 7..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 447
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 493
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 509 AA; 57715 MW; A91B7E87F76783EF CRC64;
MSIDTLLYTS LAVGAVYLAS VALYELYWSP LAHIPGPKLA ACTRLYEFFY DVVCGGQYTF
KIADLHKQYG PIIRISPREI HIHDPNYYET LYATNSPRNK DPWFTAHFGV DESAFSTLDY
RLHRSRRAMI APFFAKARMD GAQPLIKANL AKLIRHLDAH ASSQSVLKVE VAYNSFTGDV
ITGYTSYRSF EYLETTDMVP IWSETVRNLV ESGMLSRHLP GFFPLLAWAG SRCIAAVYPK
LLPVIAFRMK CAQEVNFMWT NSEEGKKEAI QSGCSEPALF PELVSRASSA PDITEERLLH
EFITIVAAGT ETTAHTMTVC TFHIAHNQSI LDKLREELDN RFHSNADMDL QTLEQLPYLT
GIIYEGLRLS YGLSHRLQRI SPIDPLKYKD IAIPPNTPVG MSSALMHHDE SIFPQSHEFI
PERWTDPNDR RRLNKYMVSF SKGSRQCIGM NLAFAELYLG IATLFRRYDM KLHDTTLDDV
QLHGDKMLPR AKNGSKGVRV TLRRAQSVG
//
