BREF5_EUPBR
ID BREF5_EUPBR Reviewed; 489 AA.
AC A0A068AA78;
DT 18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2014, sequence version 1.
DT 03-AUG-2022, entry version 19.
DE RecName: Full=Cytochrome P450 monooxygenase orf5 {ECO:0000303|PubMed:24845309};
DE EC=1.-.-.- {ECO:0000305|PubMed:24845309};
DE AltName: Full=Brefeldin A biosynthesis cluster protein orf5 {ECO:0000303|PubMed:24845309};
GN Name=orf5 {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; AIA58897.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A068AA78; -.
DR SMR; A0A068AA78; -.
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; 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 Glycoprotein; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..489
FT /note="Cytochrome P450 monooxygenase orf5"
FT /id="PRO_0000444933"
FT TRANSMEM 13..35
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 428
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 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 345
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 489 AA; 56075 MW; 65B2DF147141C3D9 CRC64;
MANDVSGLGP TAFVRLLAFH LIGLFVSITV YRLFFHNLSG FRGPFIARLS SFYLAWLSAK
RLHLHDEIDD LHSLYGDYVR TGPRELSIID PQCVQVIYGS QTKCIKGPIY TLLDPRTNLS
STRDKTEHAK RRRAWDRGFS TTALHTYEPM VQELTEELMT IIDELSENPI NITEWVDKYA
FEVMGQLTFG KPFNMLKERK EAYFLELIRQ DMNAIGYLLN LPWLSYLFLR TPGLNQNHLN
FWRWIENEFA QRIARGQRRP DVFNWLHQAY LQGPQTKSDT LKLHGDGYLV IVAGSDTTAS
TITHLLFYLA CNKALTQKLQ AQLDALEGLT DESLRDVELL DACINETLRL RPAVPAGVQR
ETPKEGIYIG NRYIPGDTIV KVPMYTLFRD PRSFEQPNEF IPERFTTRPE LVKDKSVFIP
FLTGSYACVG RRLALMEVRR AVAAILCRYD IALAPGQNEE GFLDGKIDAF TLVAAPLSLK
FTRRHQQKQ
