ID   VERC2_PENPO             Reviewed;         385 AA.
AC   A0A1V6NZ11;
DT   25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT   07-JUN-2017, sequence version 1.
DT   03-AUG-2022, entry version 14.
DE   RecName: Full=FAD-dependent monooxygenase verC2 {ECO:0000303|PubMed:34093475};
DE            EC=1.-.-.- {ECO:0000305|PubMed:34093475};
DE   AltName: Full=Cluster 4 protein C2 {ECO:0000303|PubMed:34093475};
DE   AltName: Full=Verrucosidin biosynthesis cluster protein C2 {ECO:0000303|PubMed:34093475};
GN   Name=verC2 {ECO:0000303|PubMed:34093475};
GN   Synonyms=cl4C2 {ECO:0000303|PubMed:34093475}; ORFNames=PENPOL_c002G07909;
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: FAD-dependent 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=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
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 paxM FAD-dependent monooxygenase family.
CC       {ECO:0000305}.
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DR   EMBL; MDYM01000002; OQD69870.1; -; Genomic_DNA.
DR   UniPathway; UPA00213; -.
DR   Proteomes; UP000191408; Unassembled WGS sequence.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   Gene3D; 3.50.50.60; -; 1.
DR   InterPro; IPR002938; FAD-bd.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   Pfam; PF01494; FAD_binding_3; 1.
DR   SUPFAM; SSF51905; SSF51905; 1.
PE   3: Inferred from homology;
KW   FAD; Flavoprotein; Glycoprotein; Membrane; Oxidoreductase;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..385
FT                   /note="FAD-dependent monooxygenase verC2"
FT                   /id="PRO_0000455360"
FT   TRANSMEM        365..385
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         26..27
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         39
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         50
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         218..220
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         227
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         237..241
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         298..302
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   CARBOHYD        320
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   385 AA;  43847 MW;  874DC22580697CC6 CRC64;
     MLCWELANRR KRIGPNRFGF PIAILTRQQL IEVLYTALSD KSKVKTGKKV VRIESEERRI
     TTWTEDGSEY EGELVVGADG VHSVTRSEMW RAADNQQPGF IQEEEKYSLS AEYSCIWGLS
     TPVPGIRQGE QIIRSYDRLT FLIFPSQNGC LGWFAIQKLN RKHVYPDIRP FSQKDTLARC
     EALRDLPIWN DVKFGDLLTL TEVCAMTPLE ENLFQTWNYG RILCIGDSIS KLTPNIAQGA
     NTAIEGAAAV ANGLHQLLHH NGLNQPSYDE IQEVLGRYSQ SQRKRMKKLH WISHMVTRLQ
     SREGLINKFV GRYIYSHTGN STFYLTGKMI AQGPVLNYLS TPKEIEIGLR ASFDQYGKDG
     GDMPWKTTIM FIALLTIVVL IYSFI