ID   BREF3_EUPBR             Reviewed;         513 AA.
AC   A0A068A9T2;
DT   18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2014, sequence version 1.
DT   03-AUG-2022, entry version 16.
DE   RecName: Full=Cytochrome P450 monooxygenase orf3 {ECO:0000303|PubMed:24845309};
DE            EC=1.-.-.- {ECO:0000305|PubMed:24845309};
DE   AltName: Full=Brefeldin A biosynthesis cluster protein orf3 {ECO:0000303|PubMed:24845309};
GN   Name=orf3 {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; AIA58895.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A068A9T2; -.
DR   SMR; A0A068A9T2; -.
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   PRINTS; PR00385; P450.
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..513
FT                   /note="Cytochrome P450 monooxygenase orf3"
FT                   /id="PRO_0000444931"
FT   TRANSMEM        11..31
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         455
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        211
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        351
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   513 AA;  59157 MW;  0B71AB38F0135B1C CRC64;
     MFDIYDYSPR LVALGLIAAT IIIYSFTLTV YRLFFHPLAR IPGPKLCAIT GWYEIFWDVL
     VGGQFTFKIE EWHKTYGPVM RIGPNEVHFN DPDFYNELYP TIGATYEKPA QWRWRFGCGT
     AIFDTIGHEH HAQRKAPVAA FFSRQKILQF SGFIQDQTDI LVKRIRDDHR GQVICANEAF
     DALTMDIIGY YAFGLSYNSL QYPGFKAPYR NVTADIARMV HVGAHFPWVF TILNALPEKY
     ITRLLPPMSK IFMFRKEISS QIRRIKDNKE YLDKNVNEHR TVFHEILNSN QPACELNEGR
     IYHEALSLVG AALETSKRTT ALAVYYILAT PGVEDNLRAE LTAAMPDKTK NLSVPELEAL
     PYLNAVIKEA LRLAIGVSQR MRRYSPTETI TYKDYTIPPN TVFGMCHWEQ LRDARIWDRP
     TEFLPERWLA EQPLALNGQP LNKYFVPFHR GPRMCLGKEF GMAQLNIGLA TLFRQDDIKL
     ELYETDRKDV DVVADFFVPL TVKESQGVRV LVK