ID   PYTD_ASPTN              Reviewed;         378 AA.
AC   Q0CZG8;
DT   12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT   12-AUG-2020, sequence version 2.
DT   03-AUG-2022, entry version 57.
DE   RecName: Full=Cytochrome P450 monooxygenase pytD {ECO:0000303|PubMed:32077283};
DE            EC=1.14.14.- {ECO:0000305|PubMed:32077283};
DE   AltName: Full=Pyranterreones biosynthesis cluster protein D {ECO:0000303|PubMed:32077283};
GN   Name=pytD {ECO:0000303|PubMed:32077283}; ORFNames=ATEG_00916;
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   INDUCTION, FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX   PubMed=32077283; DOI=10.1021/acs.jnatprod.9b01140;
RA   Tang S., Zhang W., Li Z., Li H., Geng C., Huang X., Lu X.;
RT   "Discovery and characterization of a PKS-NRPS hybrid in Aspergillus terreus
RT   by genome mining.";
RL   J. Nat. Prod. 83:473-480(2020).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase pytD; part of the gene cluster
CC       that mediates the biosynthesis of pyranterreones, a family of
CC       antioxidative compounds (PubMed:32077283). The first step of
CC       pyranonigrins biosynthesis is performed by the hybrid PKS-NRPS
CC       synthetase pytA that condenses 4 malonyl-CoA units ato the acetyl
CC       starter unit by the modular PKS of pytA (PubMed:32077283). The acyl
CC       chain is then connected to an L-serine through the amide bond by the
CC       modular NRPS of pytA (PubMed:32077283). A tetramic acid is formed and
CC       released from the PKS-NRPS pytA to give pyranterreone 5 with the help
CC       of the thioesterase pytI (PubMed:32077283). Pyranterreone 5 could be
CC       methylated by pytC to afford pyranterreone 6 (Probable). Both
CC       pyranterreones 5 and 6 are subsequently oxidized by the FAD-linked
CC       oxidoreductase pytB and the cytochrome P450 monooxygenase pytD to form
CC       the fused gamma-pyrone core, resulting in pyranterreones 7 and 11,
CC       respectively (PubMed:32077283). The hydroxy group at C-8 of
CC       pyranterreones 7 and 11 are dehydrated by the aspartyl protease pytH to
CC       form a delta-7 double bond to give pyranterreones 3 and 1, 2
CC       accordingly (PubMed:32077283). The exo-methylene of pyranterreone 3
CC       could be reduced into a pendant methyl by reductase pytE to provide
CC       pyranterreone 4, also known as cordylactam (Probable). Pyranterreone 4
CC       can be reconverted to pyranterreone 3 through pytB-catalyzed
CC       dehydrogenation or further oxidized to pyranterreones 9 and 10
CC       (Probable). {ECO:0000269|PubMed:32077283, ECO:0000305|PubMed:32077283}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:32077283}.
CC   -!- INDUCTION: Expression is positively regulated by the cluster-specific
CC       transcription factor pytR. {ECO:0000269|PubMed:32077283}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of most pyranterreones,
CC       but accumulates high amounts of pyranterreone 5.
CC       {ECO:0000269|PubMed:32077283}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=EAU39562.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; CH476594; EAU39562.1; ALT_SEQ; Genomic_DNA.
DR   RefSeq; XP_001211002.1; XM_001211002.1.
DR   AlphaFoldDB; Q0CZG8; -.
DR   SMR; Q0CZG8; -.
DR   STRING; 33178.CADATEAP00006332; -.
DR   EnsemblFungi; EAU39562; EAU39562; ATEG_00916.
DR   GeneID; 4355679; -.
DR   eggNOG; KOG0684; Eukaryota.
DR   HOGENOM; CLU_1189689_0_0_1; -.
DR   OrthoDB; 572303at2759; -.
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; 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.
PE   2: Evidence at transcript level;
KW   Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Reference proteome.
FT   CHAIN           1..378
FT                   /note="Cytochrome P450 monooxygenase pytD"
FT                   /id="PRO_0000450469"
FT   BINDING         321
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   378 AA;  43110 MW;  380A4E462D750E6C CRC64;
     MGLFLNKIVI PGYFSHLRSM VGSLSRGISR KATLEYYAQV ADEETAKAVD GWTCKSEAEK
     SVALFEEISF LVHKIIVRCL MGQDFYDHHV RELYDLLRTM EANVGSIWHT VLPGWVAHGP
     ARRLWRCRQR VQEIFDFRLR ERERSPEEWK KRLDYISYTL QDPATAHLSR FYGAHHTLLM
     FAAHTSTVAS ISWILLEWKS PHRLQRLREE LATHALEQSP FLDALVKETG RHYSGNSDVR
     WARKPKTLRT EVASVPESRI TIPEGTIVSI SPYLTHHDPA TWDNADTYLP ERWLADPDLA
     KKMNEGGQLR YIPFGAGSHR CPGEKMAILI AKIAVARIVQ SCDLAWGEGS SENTLGGLDF
     SKVGSPWLKG DVQVRFQV