OTAD_ASPC5
ID OTAD_ASPC5 Reviewed; 498 AA.
AC A0A1R3RGJ2; A0A1B2AIW0;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2017, sequence version 2.
DT 03-AUG-2022, entry version 20.
DE RecName: Full=Halogenase otaD {ECO:0000303|PubMed:27422838};
DE EC=1.14.14.- {ECO:0000269|PubMed:30054361};
DE AltName: Full=Ochratoxin A biosynthesis cluster protein D {ECO:0000303|PubMed:30054361};
GN Name=otaD {ECO:0000303|PubMed:30054361};
GN Synonyms=OTAhal {ECO:0000303|PubMed:27422838}; ORFNames=ASPCADRAFT_209543;
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 [GENOMIC DNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ITEM 5010;
RX PubMed=27422838; DOI=10.1128/aem.01209-16;
RA Ferrara M., Perrone G., Gambacorta L., Epifani F., Solfrizzo M., Gallo A.;
RT "Identification of a halogenase involved in the biosynthesis of ochratoxin
RT A in Aspergillus carbonarius.";
RL Appl. Environ. Microbiol. 82:5631-5641(2016).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 1-394.
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 [3]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, 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 [4]
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 [5]
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: Halogenase; part of the gene cluster that mediates the
CC biosynthesis of ochratoxin A (OTA), a mycotoxin composed of a
CC chlorinated type I polyketide dihydroisocoumarin moiety linked to L-
CC phenylalanine, and demonstrated to have nephrotoxic, immunotoxic,
CC genotoxic, neurotoxic, and teratogenic properties (PubMed:27422838,
CC PubMed:30054361). OtaD chlorinates ochratoxin B (OTB) at the C-5
CC position to form OTA (PubMed:27422838, PubMed:30054361). The pathway
CC begins with the highly reducing polyketide synthase otaA that catalyzes
CC the formation of the isocoumarin group during the initial stages of
CC biosynthesis, starting from one acetate and 4 malonate units, to
CC originate the characteristic pentaketide skeleton 7-methylmellein (7-
CC MM) of the OTA molecule. The newly identified cyclase otaY might be
CC involved in the polyketide cyclization reaction during the initial
CC steps of the OTA biosynthesis. 7-MM is then oxidized into 7-
CC carboxymellein (also called ochratoxin beta) by the cytochrome P450
CC monooxygenase otaC. The NRPS encoded by the otaB gene is involved in
CC the linking of phenylalanine to the dihydroisocoumarin ring. The
CC reaction catalyzed by NRPS results in the production of ochratoxin B
CC (OTB), which is the non-chlorinated analog of OTA and which
CC subsequently serves as the substrate of the halogenase otaD for
CC chlorination activity to form the final molecular structure of OTA,
CC containing a chlorine atom in the C-5 position of the molecule
CC (PubMed:33391201) (Probable). {ECO:0000269|PubMed:27422838,
CC ECO:0000269|PubMed:30054361, ECO:0000305|PubMed:33391201}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P95480};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:P95480};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:27422838,
CC ECO:0000269|PubMed:30054361}.
CC -!- INDUCTION: Expression is positively regulated by the cluster-specific
CC transcription factor otaR1 (PubMed:30054361, PubMed:33540740).
CC Expression is also modulated by a second regulator, otaR2, which is
CC adjacent to the biosynthetic gene cluster (PubMed:30054361).
CC {ECO:0000269|PubMed:30054361, ECO:0000269|PubMed:33540740}.
CC -!- DISRUPTION PHENOTYPE: Completely eliminates the production of
CC ochratoxin A and leads to a significant increase of ochratoxin B.
CC {ECO:0000269|PubMed:27422838, ECO:0000269|PubMed:30054361}.
CC -!- SIMILARITY: Belongs to the flavin-dependent halogenase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ANY27070.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; KU960948; ANY27070.1; ALT_SEQ; Genomic_DNA.
DR EMBL; KV907504; OOF93604.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1R3RGJ2; -.
DR SMR; A0A1R3RGJ2; -.
DR STRING; 602072.A0A1R3RGJ2; -.
DR EnsemblFungi; OOF93604; OOF93604; ASPCADRAFT_209543.
DR OrthoDB; 462247at2759; -.
DR BioCyc; MetaCyc:MON-21058; -.
DR Proteomes; UP000188318; Unassembled WGS sequence.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:1900818; P:ochratoxin A biosynthetic process; IDA:GO_Central.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Monooxygenase; Oxidoreductase; Reference proteome.
FT CHAIN 1..498
FT /note="Halogenase otaD"
FT /id="PRO_0000440594"
FT BINDING 14..17
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT BINDING 37..48
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT BINDING 326..327
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P95480"
SQ SEQUENCE 498 AA; 53895 MW; 7CA5EB5CEA8BD27E CRC64;
MAIPQKATVL VIGGGPGGSY SASALAREGI DTVVLEADVF PRYHIGESLV ASIRPFLKFI
DLDDTFVNYG FVRKNGAAFK LNNQKEAYTD FILEAGADTF AWNVVRSESD DLMFKHAAKS
GAQTFDGVRV TSIEFTDDDD DDDNNTNRPV SASWKAKDGR TGSIEFDYLV DASGRAGITS
TKYLKNRTFN NYLKNVASWG YWEGATPYGM GTPVEGQPFF EALQDGSGWV WFIPLHNNTT
SIGIVMNQEL STQKKKLSTT TSSRAFYLES LAGARGISRL LDPTTATLTS DIKHASDWSY
NASAYGSPYL RIVGDAGAFI DPYFSSGVHL AVSGGLSAAV SIAASIRGDC PEEAAWKWHS
QGVANRYGRF LLVVLGATKQ IRAGDRPVLN GVGDEGFDEA FMVIRPVIQG IADVQGKVPV
QDVYDAVTFS TNVVQPAAEG KRDPGWVEKA RGALSHDEKE VGSVLNNLAK AYKTTDVCEG
LMARLERGHL GLKLVSEV
