ID   VERH_PENPO              Reviewed;         538 AA.
AC   A0A1V6NWJ0;
DT   25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT   07-JUN-2017, sequence version 1.
DT   03-AUG-2022, entry version 13.
DE   RecName: Full=Cytochrome P450 monooxygenase verH {ECO:0000303|PubMed:34093475};
DE            EC=1.-.-.- {ECO:0000305|PubMed:34093475};
DE   AltName: Full=Cluster 4 protein H {ECO:0000303|PubMed:34093475};
DE   AltName: Full=Verrucosidin biosynthesis cluster protein H {ECO:0000303|PubMed:34093475};
GN   Name=verH {ECO:0000303|PubMed:34093475};
GN   Synonyms=cl4H {ECO:0000303|PubMed:34093475}; ORFNames=PENPOL_c002G07307;
OS   Penicillium polonicum.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=60169;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=IBT 4502;
RX   PubMed=28368369; DOI=10.1038/nmicrobiol.2017.44;
RA   Nielsen J.C., Grijseels S., Prigent S., Ji B., Dainat J., Nielsen K.F.,
RA   Frisvad J.C., Workman M., Nielsen J.;
RT   "Global analysis of biosynthetic gene clusters reveals vast potential of
RT   secondary metabolite production in Penicillium species.";
RL   Nat. Microbiol. 2:17044-17044(2017).
RN   [2]
RP   FUNCTION.
RX   PubMed=34093475; DOI=10.3389/fmicb.2021.660871;
RA   Valente S., Piombo E., Schroeckh V., Meloni G.R., Heinekamp T.,
RA   Brakhage A.A., Spadaro D.;
RT   "CRISPR-Cas9-Based Discovery of the Verrucosidin Biosynthesis Gene Cluster
RT   in Penicillium polonicum.";
RL   Front. Microbiol. 12:660871-660871(2021).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of the neurotoxin verrucosidin, a methylated
CC       alpha-pyrone polyketide that inhibits oxidative phosphorylation in
CC       mitochondria and thereby causes neurological diseases
CC       (PubMed:34093475). The carbon backbone of verrucosidin is synthesized
CC       by the HR-PKS verA, and further modified by the other verrucodidin
CC       cluster enzymes (Probable). {ECO:0000269|PubMed:34093475,
CC       ECO:0000305|PubMed:34093475}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000305|PubMed:34093475}.
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:34093475}.
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; MDYM01000002; OQD69071.1; -; Genomic_DNA.
DR   STRING; 60169.A0A1V6NWJ0; -.
DR   UniPathway; UPA00213; -.
DR   Proteomes; UP000191408; Unassembled WGS sequence.
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; 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.
PE   3: Inferred from homology;
KW   Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..538
FT                   /note="Cytochrome P450 monooxygenase verH"
FT                   /id="PRO_0000455355"
FT   TRANSMEM        2..21
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"
SQ   SEQUENCE   538 AA;  61279 MW;  9F6F0FD2B79DD8D7 CRC64;
     MVFAMLVVCW SIFLGLWMLV SRLKQSRDKI CPPKGPPRLP WIGNLHQFPL KLLHLRLTEW
     SRTYGGFYTL KLGPVTAAVI TDRQIAKEAF DRNSAISSTR HTNYATEFVT DGTHLLTMKY
     GALWREERKI LQQTLKGSVC DNDHMRLIDA EQTQLMRDLL VNPSDYSAYI KRASTSIITS
     LVFGIRTPSC ATLHLQELDA INDDWLQLLV IGGALSEDVF PVLKYIPSAF LGTFTKRLKG
     IRRRMRRLYG TMLNQTITRQ RESPAPPARS MIDAVLNQRE HFNLTDRQIE VLAGVTLEGG
     FDTTTSMLLV FVQAMTLHPE CQERAYVEIN ALCGRHRIPQ WSDRNQLPYV NMLLKETMRW
     RPVTTLSPPH VLEKDTTIRG TFLPQGSMLI LNTWGLHQDP NVFIDPDRFD PMRYEGYTKL
     AADYANAPDA ATRDHYTYGI GRRICPGIHL ADRSMFLAIA KLIWGFRFEP QRDEQGNSIP
     IDSNPVTGYT VDKVQISPKP FACAVIPRDK EGEKTILREF GVASEVFADY NLDENASL