ID   BREF6_EUPBR             Reviewed;         502 AA.
AC   A0A068ACU3;
DT   18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2014, sequence version 1.
DT   03-AUG-2022, entry version 18.
DE   RecName: Full=Cytochrome P450 monooxygenase orf6 {ECO:0000303|PubMed:24845309};
DE            EC=1.-.-.- {ECO:0000305|PubMed:24845309};
DE   AltName: Full=Brefeldin A biosynthesis cluster protein orf6 {ECO:0000303|PubMed:24845309};
GN   Name=orf6 {ECO:0000303|PubMed:24845309};
OS   Eupenicillium brefeldianum (Penicillium brefeldianum).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=1131482;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND INDUCTION.
RC   STRAIN=ATCC 58665;
RX   PubMed=24845309; DOI=10.1021/cb500284t;
RA   Zabala A.O., Chooi Y.H., Choi M.S., Lin H.C., Tang Y.;
RT   "Fungal polyketide synthase product chain-length control by partnering
RT   thiohydrolase.";
RL   ACS Chem. Biol. 9:1576-1586(2014).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of brefeldin A (BFA), a protein transport
CC       inhibitor that shows antiviral, antifungal, and antitumor properties
CC       (PubMed:24845309). The proposed biosynthesis of BFA involves formation
CC       of an acyclic polyketide chain that is differentially tailored
CC       throughout the backbone (PubMed:24845309). The highly reducing
CC       polyketide synthase Bref-PKS is proposed to synthesize the precisely
CC       reduced octaketide precursor, which could then be directly offloaded by
CC       the thiohydrolase enzyme Bref-TH followed by a cytochrome P450
CC       monooxygenase-mediated formation of the cyclopentane ring and
CC       macrocyclization to afford 7-deoxy BFA. Alternatively, the first ring
CC       annulation can also occur on the ACP-tethered intermediate before the
CC       thiohydrolase release and lactonization (PubMed:24845309). The C7-
CC       hydroxylation by another cytochrome P450 monooxygenase is believed to
CC       be the final step in the process to obtain the final structure of BFA
CC       (PubMed:24845309). In addition to the HRPKS Bref-PKS and the
CC       thiohydrolase Bref-TH, the brefeldin A biosynthesis cluster contains 4
CC       cytochrome p450 monooxygenases (called orf3 to orf6), as well a the
CC       probable cluster-specific transcription regulator orf8
CC       (PubMed:24845309). {ECO:0000269|PubMed:24845309}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:24845309}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- INDUCTION: Coexpressed with the other cluster genes on brefeldin A
CC       production optimized medium. {ECO:0000269|PubMed:24845309}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; KJ728786; AIA58898.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A068ACU3; -.
DR   SMR; A0A068ACU3; -.
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   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   SUPFAM; SSF48264; SSF48264; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   2: Evidence at transcript level;
KW   Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW   Oxidoreductase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..502
FT                   /note="Cytochrome P450 monooxygenase orf6"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000444934"
FT   TRANSMEM        3..25
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         445
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"
FT   CARBOHYD        382
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   502 AA;  57665 MW;  7B630835C975E5B7 CRC64;
     MLALWVLAVA LVAYFLCLSI YRLFLHPLAN IPGPKLCALT GWYEVFWDIV VGGQFTFKIE
     EWHKTYGPVM RIGPNEVHFN DPDFYNELYT TTAAYQKPAE WRYRFGFGSA LFDTVDHEHH
     AKRRAPLAAF FSRSKILEFS PFIQEQTDLL VQRIQEYEGQ VICANEAFDA LTMDIIGYYA
     FGLSYRSIDY PKFQAPCNHV TEDVARMVHT GAHFPWVFTI LRSIPQAIVS LLAPPMKKIF
     KFNEEIAAQI RRILKNRVNL DQEKNFHRTI FHEILNSKLD PSELTQERLQ MEAGSLVGAA
     LETSKMTTAL AIYYILAQPD VEKKLREELR TAMPDPGKIL SVPELEQLPY LAACIREALR
     LAIGVSQRIR RYNPHAPTQY KNYTIPPNTV FGMCHWEQLR DARVWDRPYE FLPERWLANN
     GNPLALNGQP LAKYFVPFHR GPRGCLGKEM GMAQLNIGLA TLFRRVDHLE LFETDQSAVD
     IVADYFVPLC VKGSKGVRVL VK