OTAC_ASPC5
ID OTAC_ASPC5 Reviewed; 516 AA.
AC A0A1R3RGJ7;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2017, sequence version 1.
DT 03-AUG-2022, entry version 15.
DE RecName: Full=Cytochrome P450 monooxygenase otaC {ECO:0000303|PubMed:30054361};
DE EC=1.-.-.- {ECO:0000305|PubMed:30054361};
DE AltName: Full=Ochratoxin A biosynthesis cluster protein C {ECO:0000303|PubMed:30054361};
GN Name=otaC {ECO:0000303|PubMed:30054361};
GN Synonyms=OTAp450 {ECO:0000303|PubMed:33540740}; ORFNames=ASPCADRAFT_517149;
OS Aspergillus carbonarius (strain ITEM 5010).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=602072;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ITEM 5010;
RX PubMed=28196534; DOI=10.1186/s13059-017-1151-0;
RA de Vries R.P., Riley R., Wiebenga A., Aguilar-Osorio G., Amillis S.,
RA Uchima C.A., Anderluh G., Asadollahi M., Askin M., Barry K., Battaglia E.,
RA Bayram O., Benocci T., Braus-Stromeyer S.A., Caldana C., Canovas D.,
RA Cerqueira G.C., Chen F., Chen W., Choi C., Clum A., Dos Santos R.A.,
RA Damasio A.R., Diallinas G., Emri T., Fekete E., Flipphi M., Freyberg S.,
RA Gallo A., Gournas C., Habgood R., Hainaut M., Harispe M.L., Henrissat B.,
RA Hilden K.S., Hope R., Hossain A., Karabika E., Karaffa L., Karanyi Z.,
RA Krasevec N., Kuo A., Kusch H., LaButti K., Lagendijk E.L., Lapidus A.,
RA Levasseur A., Lindquist E., Lipzen A., Logrieco A.F., MacCabe A.,
RA Maekelae M.R., Malavazi I., Melin P., Meyer V., Mielnichuk N., Miskei M.,
RA Molnar A.P., Mule G., Ngan C.Y., Orejas M., Orosz E., Ouedraogo J.P.,
RA Overkamp K.M., Park H.-S., Perrone G., Piumi F., Punt P.J., Ram A.F.,
RA Ramon A., Rauscher S., Record E., Riano-Pachon D.M., Robert V., Roehrig J.,
RA Ruller R., Salamov A., Salih N.S., Samson R.A., Sandor E., Sanguinetti M.,
RA Schuetze T., Sepcic K., Shelest E., Sherlock G., Sophianopoulou V.,
RA Squina F.M., Sun H., Susca A., Todd R.B., Tsang A., Unkles S.E.,
RA van de Wiele N., van Rossen-Uffink D., Oliveira J.V., Vesth T.C.,
RA Visser J., Yu J.-H., Zhou M., Andersen M.R., Archer D.B., Baker S.E.,
RA Benoit I., Brakhage A.A., Braus G.H., Fischer R., Frisvad J.C.,
RA Goldman G.H., Houbraken J., Oakley B., Pocsi I., Scazzocchio C.,
RA Seiboth B., vanKuyk P.A., Wortman J., Dyer P.S., Grigoriev I.V.;
RT "Comparative genomics reveals high biological diversity and specific
RT adaptations in the industrially and medically important fungal genus
RT Aspergillus.";
RL Genome Biol. 18:RESEARCH28.1-RESEARCH28.45(2017).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, INDUCTION, AND PATHWAY.
RX PubMed=30054361; DOI=10.1128/aem.01009-18;
RA Wang Y., Wang L., Wu F., Liu F., Wang Q., Zhang X., Selvaraj J.N., Zhao Y.,
RA Xing F., Yin W.B., Liu Y.;
RT "A consensus ochratoxin A biosynthetic pathway: insights from the genome
RT sequence of Aspergillus ochraceus and a comparative genomic analysis.";
RL Appl. Environ. Microbiol. 84:0-0(2018).
RN [3]
RP 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 [4]
RP INDUCTION.
RX PubMed=33540740; DOI=10.3390/toxins13020111;
RA Gerin D., Garrapa F., Ballester A.R., Gonzalez-Candelas L.,
RA De Miccolis Angelini R.M., Faretra F., Pollastro S.;
RT "Functional role of Aspergillus carbonarius AcOTAbZIP gene, a bZIP
RT transcription factor within the OTA gene cluster.";
RL Toxins 13:0-0(2021).
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:30054361).
CC OtaC catalyzes the oxidation of 7-methylmellein (7-MM) into 7-
CC carboxymellein (PubMed:30054361). 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:33391201) (Probable). {ECO:0000269|PubMed:30054361,
CC ECO:0000305|PubMed:33391201}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:30054361}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is positively regulated by the cluster-specific
CC transcription factor otaR1. {ECO:0000269|PubMed:30054361,
CC ECO:0000269|PubMed:33540740}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of ochratoxin A as well
CC as of its intermediates ochratoxin B and ochratoxin beta.
CC {ECO:0000269|PubMed:30054361}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KV907504; OOF93602.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1R3RGJ7; -.
DR SMR; A0A1R3RGJ7; -.
DR STRING; 602072.A0A1R3RGJ7; -.
DR EnsemblFungi; OOF93602; OOF93602; ASPCADRAFT_517149.
DR VEuPathDB; FungiDB:ASPCADRAFT_517149; -.
DR OrthoDB; 1247045at2759; -.
DR BioCyc; MetaCyc:MON-21060; -.
DR Proteomes; UP000188318; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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: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; IMP:GO_Central.
DR Gene3D; 1.10.630.10; -; 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 Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 2: Evidence at transcript level;
KW Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..516
FT /note="Cytochrome P450 monooxygenase otaC"
FT /evidence="ECO:0000255"
FT /id="PRO_0000440590"
FT TRANSMEM 13..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 454
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"
SQ SEQUENCE 516 AA; 58623 MW; D39FFA86F1B26735 CRC64;
MNMDSIASFS HPFLWTAFAV GVVYCCTRMV SELFLSPLSH IPGPKLAACT RLYEFFYDVI
CHGRYTFKIA ELHEKYGPIV RISPTEIHIN DPEFYETLYS TSAPRNKDPW FTTNFDVAES
AFSTLDYRLH RPRRALIAPY FAKARVDRIQ PLIQGKITKL MRQLDEYARA GKPLKVDVAY
NCFTADVITG YTSYRPLGYL DTPDMVPIWS ETVRNLVEIG MIARHLPGFF PLLASTGARC
IQMVYPKLLS VIAFRVKCIQ EVNFMWTHPE TATKDAAQAE CSEPALFPEL VSRASTTPDI
TEERVLHEFI TIVAAGTETT AHTMTVCTFH ILNNKDILRR LRAELNDKFP GDATMDLQTL
EQLPYLTGII YEGLRLSYGL SHRLQRISPT DPLKYKDVVI PPNTPVGMSS ALIHHDETIF
PQSHAFIPDR WTDINERRRL NKYMVAFSKG SRQCIGMNLA FAELYMAVAA LFRKYDMELQ
DTTVDDVKLH SDMMLPHAKK GSKGVRVILK PAQGGE
