ID   ATAY_ASPTN              Reviewed;         228 AA.
AC   Q0CS66;
DT   05-JUL-2017, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 1.
DT   03-AUG-2022, entry version 59.
DE   RecName: Full=Cytochrome P450 monooxygenase ataY {ECO:0000303|PubMed:23586797};
DE            EC=1.-.-.- {ECO:0000305|PubMed:23586797};
DE   AltName: Full=Acetylaranotin biosynthesis cluster protein Y {ECO:0000303|PubMed:23586797};
GN   Name=ataY {ECO:0000303|PubMed:23586797}; ORFNames=ATEG_03468;
OS   Aspergillus terreus (strain NIH 2624 / FGSC A1156).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=341663;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=NIH 2624 / FGSC A1156;
RA   Birren B.W., Lander E.S., Galagan J.E., Nusbaum C., Devon K., Henn M.,
RA   Ma L.-J., Jaffe D.B., Butler J., Alvarez P., Gnerre S., Grabherr M.,
RA   Kleber M., Mauceli E.W., Brockman W., Rounsley S., Young S.K., LaButti K.,
RA   Pushparaj V., DeCaprio D., Crawford M., Koehrsen M., Engels R.,
RA   Montgomery P., Pearson M., Howarth C., Larson L., Luoma S., White J.,
RA   Alvarado L., Kodira C.D., Zeng Q., Oleary S., Yandava C., Denning D.W.,
RA   Nierman W.C., Milne T., Madden K.;
RT   "Annotation of the Aspergillus terreus NIH2624 genome.";
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX   PubMed=23586797; DOI=10.1021/ja3123653;
RA   Guo C.J., Yeh H.H., Chiang Y.M., Sanchez J.F., Chang S.L., Bruno K.S.,
RA   Wang C.C.;
RT   "Biosynthetic pathway for the epipolythiodioxopiperazine acetylaranotin in
RT   Aspergillus terreus revealed by genome-based deletion analysis.";
RL   J. Am. Chem. Soc. 135:7205-7213(2013).
RN   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=30096370; DOI=10.1016/j.fgb.2018.08.001;
RA   Sun W.W., Romsdahl J., Guo C.J., Wang C.C.C.;
RT   "Genome-based deletion analysis in Aspergillus terreus reveals the
RT   acetylaranotin bis-thiomethyltransferase gene.";
RL   Fungal Genet. Biol. 119:1-6(2018).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of acetylaranotin, a member of the
CC       epipolythiodioxopiperazine (ETP) class of toxins characterized by a
CC       disulfide-bridged cyclic dipeptide (PubMed:23586797). The first step of
CC       acetylaranotin biosynthesis is performed by the NRPS ataP which
CC       produces diketopiperazine cyclo-L-Phe-L-Phe via the condensation of 2
CC       phenylalanines (L-Phe) (PubMed:23586797). The ataC domain of ataTC then
CC       catalyzes the formation of bishydroxylation of cyclo-L-Phe-L-Phe
CC       (PubMed:23586797). The glutathione S-transferase domain ataG in ataIMG
CC       further catalyzes the conjugation of two glutathiones to the
CC       bishydroxylated intermediate (PubMed:23586797). Next, the dipeptidase
CC       ataJ removes the Glu residues (PubMed:23586797). The following step is
CC       performed by the carbon sulfur lyase domain ataI of ataIMG which may
CC       convert the bis-cysteinyl adduct to yield an epidithiol intermediate
CC       (PubMed:23586797). The ataT domain from ataTC then catalyzes the
CC       oxidation of the free dithiols, followed by a cyclization step
CC       catalyzed by the cytochrome P450 ataF (PubMed:23586797). AtaF probably
CC       acts as an epoxidase to promote a dual epoxidation formation at C8 and
CC       C9 along with C8' and C9', followed by the spontaneous nucleophilic
CC       attack of the amide nitrogens N10 and N10' to yield an intermediate
CC       with the pyrrolidine partial structure (PubMed:23586797). The final
CC       steps of acetylaranotin biosynthesis involve the acetylation and ring
CC       rearrangement of an epitetrathiodiketopiperazine intermediate to
CC       produce acetylaranotin (PubMed:23586797). AtaH probably catalyzes the
CC       acetylation of epitetrathiodiketopiperazine to produce a diacetate and
CC       ataY is responsible for the formation of the dihydrooxepin moiety that
CC       converts the diacetate intermediate to acetylaranotin via
CC       acetylapoaranotin (PubMed:23586797). Both enzymes could function
CC       independently in the absence of the other (PubMed:23586797). The
CC       acetylaranotin bis-thiomethyltransferase ataS located outside of
CC       acetylaranotin gene cluster is the main thiomethyltransferase
CC       responsible for converting acetylaranotin and its related intermediates
CC       to their methylated forms (PubMed:30096370).
CC       {ECO:0000269|PubMed:23586797, ECO:0000269|PubMed:30096370}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:23586797}.
CC   -!- DISRUPTION PHENOTYPE: Impairs the production of acetylaranotin and
CC       accumulates chemically stable intermediates or shunt products such as
CC       haematocin B, haematocin, terrespirodione A and terrespirodione B
CC       (PubMed:23586797, PubMed:30096370). Leads also to the accumulation of
CC       deacetylhaematocin and demethyl-deacetylhaematocin when ataS and ataH
CC       are also deleted (PubMed:30096370). {ECO:0000269|PubMed:23586797,
CC       ECO:0000269|PubMed:30096370}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; CH476597; EAU36742.1; -; Genomic_DNA.
DR   RefSeq; XP_001212646.1; XM_001212646.1.
DR   AlphaFoldDB; Q0CS66; -.
DR   SMR; Q0CS66; -.
DR   EnsemblFungi; EAU36742; EAU36742; ATEG_03468.
DR   GeneID; 4318081; -.
DR   VEuPathDB; FungiDB:ATEG_03468; -.
DR   eggNOG; KOG0158; Eukaryota.
DR   HOGENOM; CLU_1214522_0_0_1; -.
DR   OMA; ETYITIY; -.
DR   OrthoDB; 1247045at2759; -.
DR   Proteomes; UP000007963; Unassembled WGS sequence.
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   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   SUPFAM; SSF48264; SSF48264; 1.
PE   3: Inferred from homology;
KW   Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Reference proteome.
FT   CHAIN           1..228
FT                   /note="Cytochrome P450 monooxygenase ataY"
FT                   /id="PRO_0000440658"
FT   BINDING         216
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:0000305"
SQ   SEQUENCE   228 AA;  26176 MW;  C1DC3F845425375A CRC64;
     MYGPGTKFEK AMFYTRGPKE KQLLVNLAST TDKAVHARKR RIISHALSEA SIRSYEVTIL
     DKIQLFCKQL SDASTFGGPY KNMSRWFSYL TYDIMGQLTF SQSYDMLTKD DHHFIQPLID
     SYQHSQLGTE PKLDQWGLAP LLLLRIMAEN KKFRRYVDDQ VNHRIALEKA GQGPPDIFKL
     LLEHKDKETG ESMGFKELSD EAVVLIIAGR RFFSPCVNGS KRFTLNSQ