OTAD_ASPNC
ID OTAD_ASPNC Reviewed; 476 AA.
AC A2R6G7;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Halogenase otaD {ECO:0000303|PubMed:33391201};
DE EC=1.14.14.- {ECO:0000250|UniProtKB:A0A1R3RGJ2};
DE AltName: Full=Ochratoxin biosynthesis cluster protein 5 {ECO:0000303|PubMed:27667988};
DE AltName: Full=Ochratoxin biosynthesis cluster protein D {ECO:0000303|PubMed:33391201};
GN Name=otaD {ECO:0000303|PubMed:33391201};
GN Synonyms=ota5 {ECO:0000303|PubMed:27667988}; ORFNames=An15g07880;
OS Aspergillus niger (strain 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=CBS 513.88 / FGSC A1513 / ATCC MYA-4892;
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).
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:27667988,
CC PubMed:33391201). OtaD chlorinates ochratoxin B (OTB) at the C-5
CC position to form OTA (By similarity). The pathway begins with the
CC highly reducing polyketide synthase otaA that catalyzes the formation
CC of the isocoumarin group during the initial stages of biosynthesis,
CC starting from one acetate and 4 malonate units, to originate the
CC characteristic pentaketide skeleton 7-methylmellein (7-MM) of the OTA
CC molecule. The newly identified cyclase otaY might be involved in the
CC polyketide cyclization reaction during the initial steps of the OTA
CC biosynthesis. 7-MM is then oxidized into 7-carboxymellein (also called
CC ochratoxin beta) by the cytochrome P450 monooxygenase otaC. The NRPS
CC encoded by the otaB gene is involved in the linking of phenylalanine to
CC the dihydroisocoumarin ring. The reaction catalyzed by NRPS results in
CC the production of ochratoxin B (OTB), which is the non-chlorinated
CC analog of OTA and which subsequently serves as the substrate of the
CC halogenase otaD for chlorination activity to form the final molecular
CC structure of OTA, containing a chlorine atom in the C-5 position of the
CC molecule (PubMed:27667988, PubMed:33391201) (Probable).
CC {ECO:0000250|UniProtKB:A0A1R3RGJ2, ECO:0000269|PubMed:27667988,
CC ECO:0000269|PubMed:33391201, ECO:0000305|PubMed:27667988,
CC 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:0000250|UniProtKB:A0A1R3RGJ2}.
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. {ECO:0000269|PubMed:35143724}.
CC -!- SIMILARITY: Belongs to the flavin-dependent halogenase family.
CC {ECO:0000305}.
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DR EMBL; AM270352; CAK42675.1; -; Genomic_DNA.
DR AlphaFoldDB; A2R6G7; -.
DR SMR; A2R6G7; -.
DR PaxDb; A2R6G7; -.
DR EnsemblFungi; CAK42675; CAK42675; An15g07880.
DR VEuPathDB; FungiDB:An15g07880; -.
DR HOGENOM; CLU_024648_4_2_1; -.
DR Proteomes; UP000006706; Chromosome 3R.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:1900818; P:ochratoxin A biosynthetic process; ISS:GO_Central.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR006905; Flavin_halogenase.
DR Pfam; PF04820; Trp_halogenase; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 2: Evidence at transcript level;
KW FAD; Flavoprotein; Monooxygenase; Oxidoreductase; Reference proteome.
FT CHAIN 1..476
FT /note="Halogenase otaD"
FT /id="PRO_0000440595"
FT BINDING 14..17
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT BINDING 304..305
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P95480"
SQ SEQUENCE 476 AA; 51015 MW; 7E206B72F1EA4F9C CRC64;
MEIPHKATVL VIGGGPGGSY TASALAREGI DIVLLEADVF PRFIDLDETF VNYGFVRKNA
SHGSLADTDF ILQPGADTFA WNVVRSECDD LMFKHASNSG ARAFDGVKVT AIEFDPLDES
AIDDHPGRPV SASWKAKDGR TGSISFDYLV DASGRAGIAS TKYLKSRTYN SYLKNVASWG
YWRGATPYGV GTSVEGQPYF EALQDGSGWV WFIPLHNGTT SVGVVMNQEL ATQKKKSSTV
TSSRAFYLES VEGARVISQL LQPANLDGEI KQASDWSYNA SSYGSPYLRI VGDAGAFIDP
YFSSGVHLAV SGGLSAAVSI AASIRGDCPE HTAWQWHSQG VANRYGRFLL VVLGATKQIR
ARDSPVLNSE GQDGFDDAFA VIRPVIQGTA DVQGKVSARE VLDAVTFSTN AVRPSAGGQN
VVLEESSRSL RSQVEQEMGD VANSLAKAYK DTDVYEGLMA RLERGSLGLK AVGVMG
