ID   AP450_ASPUT             Reviewed;         548 AA.
AC   P9WEP1; A0A889ZB34;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   29-SEP-2021, sequence version 1.
DT   03-AUG-2022, entry version 4.
DE   RecName: Full=Aspergilol synthase AuAP450 {ECO:0000303|PubMed:33480256};
DE            EC=1.-.-.- {ECO:0000269|PubMed:33480256};
DE   AltName: Full=Aspergilols biosynthesis cluster protein AuAP450 {ECO:0000303|PubMed:33480256};
DE   AltName: Full=Cytochrome P450 monooxygenase AuAP450 {ECO:0000303|PubMed:33480256};
GN   Name=AuAP450 {ECO:0000303|PubMed:33480256};
OS   Aspergillus ustus.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX   NCBI_TaxID=40382;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND
RP   BIOTECHNOLOGY.
RX   PubMed=33480256; DOI=10.1021/acs.orglett.0c03996;
RA   Guo J., Cai Y.S., Cheng F., Yang C., Zhang W., Yu W., Yan J., Deng Z.,
RA   Hong K.;
RT   "Genome mining Reveals a multiproduct sesterterpenoid biosynthetic gene
RT   cluster in Aspergillus ustus.";
RL   Org. Lett. 23:1525-1529(2021).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of aspergiltriene A, aspergildienes A-D and
CC       aspergilols A-D (PubMed:33480256). The bifunctional terpene synthase
CC       AuAS converts DMAPP and IPP into sesterterpenes (PubMed:33480256). The
CC       C-terminal prenyltransferase (PT) domain of AuAS catalyzes formation of
CC       GFPP, whereas the N-terminal terpene cyclase (TC) domain catalyzes the
CC       cyclization of GFPP into 5 distinct sesterterpenes: aspergiltriene A,
CC       aspergildiene A, aspergildiene B, aspergildiene C and aspergildiene D
CC       (PubMed:33480256). The cytochrome P450 monooxygenase AP450 then
CC       hydroxylates the aspergildienes A, B, C and D to yield the
CC       corresponding sesterterpene alcohols, aspergilols A-D
CC       (PubMed:33480256). {ECO:0000269|PubMed:33480256}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:33480256}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- BIOTECHNOLOGY: Aspergilol A shows a weak cytotoxicity toward MCF-7,
CC       MDA-MB231, and HepG2 cancer cells lines, with an IC(50) value ranging
CC       from 21.21 to 48.76 uM; whereas aspergilol B only shows a weak
CC       cytotoxicity against MCF-7 cells, with an IC(50) value of 27.41 uM
CC       (PubMed:33480256). None of the aspergilols have antifungal or
CC       antibacterial activities (PubMed:33480256).
CC       {ECO:0000269|PubMed:33480256}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; MW387951; QRF92543.1; -; mRNA.
DR   SMR; P9WEP1; -.
DR   UniPathway; UPA00213; -.
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:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00465; EP450IV.
DR   SUPFAM; SSF48264; SSF48264; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   1: Evidence at protein level;
KW   Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..548
FT                   /note="Aspergilol synthase AuAP450"
FT                   /id="PRO_0000453708"
FT   TRANSMEM        38..58
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         489
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   548 AA;  63447 MW;  BAE5BABF290193B2 CRC64;
     MDIYVVGPFG HAMDLLPNPT RPFSGRLHEL SALALQRPQL VITTLGALLL AAFYLLPSKD
     PYNLKRIPMV SRSRVLDAYR SGVWWRFILP RFYPYIHEGY LKYSTKDRPF RVWLAQFQIW
     VYILPLKYLP LVKNQGITEL SLRDFIDKAT SAQLSSGSFD TFEVQVGSKL LNGNLIDIKP
     IVQTRTEQIL ERVIGRPREW RRFNIRALSV QVVKHVSARI AFGEALADNP GFLDAMERYS
     LNVIPYTLVF RYFNLGPLRY PLLYLIHLRQ RQTLAVATRY VTDLIAERQR KEKEHRLDGD
     ERPVDCIQWS MDQDIPDEQK APEAVAHRLL HISAALIDAP ITSMMNVLAD IISYARDEVL
     DDLRAEIVEC LAEFDGAWTE ASMAKMKKLD SFFQESFRMT SGLIPLTGWR LIKADCFRFD
     NDLVLPRGST IVFPTQCIQL DPNIYPNPDK FDYLRFYRMK EHTQSTDART GKEVPRHEWL
     SFGHGRQACP GRFYSIRLLK TILGEMMLRY DIRYAGGDRP RPPMIDLEPI LAPDTSVELE
     FRVRQNVT