ID   PVHE_TALVA              Reviewed;         539 AA.
AC   A0A3S5HYN5;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   10-APR-2019, sequence version 1.
DT   03-AUG-2022, entry version 8.
DE   RecName: Full=Cytochrome P450 monooxygenase pvhE {ECO:0000303|PubMed:30609896};
DE            EC=1.-.-.- {ECO:0000269|PubMed:30609896};
DE   AltName: Full=Varicidin biosynthesis cluster protein E {ECO:0000303|PubMed:30609896};
GN   Name=pvhE {ECO:0000303|PubMed:30609896};
OS   Talaromyces variabilis (Penicillium variabile).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces.
OX   NCBI_TaxID=28576;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP   PATHWAY.
RC   STRAIN=HXQ-H-1;
RX   PubMed=30609896; DOI=10.1021/jacs.8b12010;
RA   Tan D., Jamieson C.S., Ohashi M., Tang M.C., Houk K.N., Tang Y.;
RT   "Genome-mined Diels-Alderase catalyzes formation of the cis-
RT   octahydrodecalins of varicidin A and B.";
RL   J. Am. Chem. Soc. 141:769-773(2019).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of varicidin A, an antifungal natural product
CC       containing a cis-octahydrodecalin core (PubMed:30609896). The PKS
CC       module of pvhA together with the enoylreductase pvhC catalyze the
CC       formation of the polyketide unit which is then conjugated to L-
CC       isoleucine by the condensation domain of the NRPS module
CC       (PubMed:30609896). Activity of the Dieckmann cyclase domain (RED) of
CC       pvhA results in release of an acyclic tetramate (PubMed:30609896). The
CC       cytochrome P450 monooxygenase pvhE then catalyzes the oxidation of the
CC       C21 methyl group to a to carboxylate group (PubMed:30609896). The
CC       methyltransferase pvhD then further methylates the pvhE product
CC       (PubMed:30609896). The Diels-Alderase pvhB is able to catalyzes Diels-
CC       Alder cycloaddition using both pvhE and pvhD products as substrates to
CC       form the decalin ring, yielding varicidin B and A, respectively
CC       (PubMed:30609896). {ECO:0000269|PubMed:30609896}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:30609896}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; MK376933; AZZ09610.1; -; Genomic_DNA.
DR   SMR; A0A3S5HYN5; -.
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   1: Evidence at protein level;
KW   Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW   Oxidoreductase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..539
FT                   /note="Cytochrome P450 monooxygenase pvhE"
FT                   /id="PRO_0000453347"
FT   TRANSMEM        15..31
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         473
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        379
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   539 AA;  61255 MW;  005645EAC2D0E884 CRC64;
     MSVLNIAVSR CSPTVAFCSL VILCILFKVL TRVREDRKIR SLGKYGHQIQ SKLPLGIGFL
     YSMVKAVRAQ KNFEFWRDNI FGASGRWTVE TRIMNERTIF TADPGNIKAM LATQFSDYGK
     GAAFHAMWKD FLGNSIFATD GERWSASRKL IRPQFTRDRL SDLQCFEAHM QTLFRVLDAG
     GSPLDSKHAE ETPMSQGKAI DIRDLLYRFT FDVSTDFLLG QDVQSLTTPR QEFAHAFDEV
     QRMQTIFVRS RHFSKFMSKK SFRDSLKVMN GFIHKHVRRA LSLSPQETQQ KSQSGSKYTF
     LEAIAGFTRD PTMLRDQIVG VLLAGRDTTA ATLSWALYEL SRHPEAVDAL RREILQTVGS
     DAPTYDQLKN MPYLKAVLNE TLRIYPAVPY NVRIALEDTT LPHGGGPDGS EPIAVLKNTK
     IAYSTLILHR RRDLYPATSE KFADPAIFSP DRWLHWHPSA HDYIPFSAGP RLCTGQQFAL
     MEMSYVLCRL FQRFERVESH MQHIDGGNPT LKADIILSPG DGVWVSFHEP KQIDSNQLL