ID   ORF7_PENRF              Reviewed;         186 AA.
AC   W6Q4S2;
DT   07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   03-AUG-2022, entry version 21.
DE   RecName: Full=PR-toxin biosynthesis cluster protein 7 {ECO:0000303|PubMed:27921136};
GN   Name=ORF7 {ECO:0000303|PubMed:27921136}; ORFNames=PROQFM164_S02g001470;
OS   Penicillium roqueforti (strain FM164).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=1365484;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=FM164;
RX   PubMed=24407037; DOI=10.1038/ncomms3876;
RA   Cheeseman K., Ropars J., Renault P., Dupont J., Gouzy J., Branca A.,
RA   Abraham A.L., Ceppi M., Conseiller E., Debuchy R., Malagnac F., Goarin A.,
RA   Silar P., Lacoste S., Sallet E., Bensimon A., Giraud T., Brygoo Y.;
RT   "Multiple recent horizontal transfers of a large genomic region in cheese
RT   making fungi.";
RL   Nat. Commun. 5:2876-2876(2014).
RN   [2]
RP   FUNCTION.
RX   PubMed=16345540; DOI=10.1128/aem.39.4.770-776.1980;
RA   Moreau S., Lablache-Combier A., Biguet J.;
RT   "Production of eremofortins A, B, and C relative to formation of PR toxin
RT   by Penicillium roqueforti.";
RL   Appl. Environ. Microbiol. 39:770-776(1980).
RN   [3]
RP   FUNCTION.
RX   PubMed=8440737; DOI=10.1016/S0021-9258(18)53644-9;
RA   Proctor R.H., Hohn T.M.;
RT   "Aristolochene synthase. Isolation, characterization, and bacterial
RT   expression of a sesquiterpenoid biosynthetic gene (Ari1) from Penicillium
RT   roqueforti.";
RL   J. Biol. Chem. 268:4543-4548(1993).
RN   [4]
RP   FUNCTION.
RX   PubMed=15186158; DOI=10.1021/ja0499593;
RA   Felicetti B., Cane D.E.;
RT   "Aristolochene synthase: mechanistic analysis of active site residues by
RT   site-directed mutagenesis.";
RL   J. Am. Chem. Soc. 126:7212-7221(2004).
RN   [5]
RP   FUNCTION.
RX   PubMed=24239699; DOI=10.1016/j.fgb.2013.10.009;
RA   Hidalgo P.I., Ullan R.V., Albillos S.M., Montero O., Fernandez-Bodega M.A.,
RA   Garcia-Estrada C., Fernandez-Aguado M., Martin J.F.;
RT   "Molecular characterization of the PR-toxin gene cluster in Penicillium
RT   roqueforti and Penicillium chrysogenum: cross talk of secondary metabolite
RT   pathways.";
RL   Fungal Genet. Biol. 62:11-24(2014).
RN   [6]
RP   FUNCTION.
RX   PubMed=26274339; DOI=10.1002/anie.201506128;
RA   Riclea R., Dickschat J.S.;
RT   "Identification of intermediates in the biosynthesis of PR toxin by
RT   Penicillium roqueforti.";
RL   Angew. Chem. Int. Ed. 54:12167-12170(2015).
RN   [7]
RP   FUNCTION, AND PATHWAY.
RX   PubMed=27921136; DOI=10.1007/s00253-016-7995-5;
RA   Hidalgo P.I., Poirier E., Ullan R.V., Piqueras J., Meslet-Cladiere L.,
RA   Coton E., Coton M.;
RT   "Penicillium roqueforti PR toxin gene cluster characterization.";
RL   Appl. Microbiol. Biotechnol. 101:2043-2056(2017).
CC   -!- FUNCTION: Part of the gene cluster that mediates the biosynthesis of
CC       PR-toxin, a bicyclic sesquiterpene belonging to the eremophilane class
CC       and acting as a mycotoxin (PubMed:24239699, PubMed:27921136). The first
CC       step of the pathway is catalyzed by the aristolochene synthase which
CC       performs the cyclization of trans,trans-farnesyl diphosphate (FPP) to
CC       the bicyclic sesquiterpene aristolochene (PubMed:8440737,
CC       PubMed:15186158, PubMed:24239699). Following the formation of
CC       aristolochene, the non-oxygenated aristolochene is converted to the
CC       trioxygenated intermediate eremofortin B, via 7-epi-neopetasone
CC       (PubMed:24239699, PubMed:26274339). This conversion appears to involve
CC       three enzymes, a hydroxysterol oxidase-like enzyme, the quinone-oxidase
CC       prx3 that forms the quinone-type-structure in the bicyclic nucleus of
CC       aristolochene with the C8-oxo group and the C-3 hydroxyl group, and the
CC       P450 monooxygenase ORF6 that introduces the epoxide at the double bond
CC       between carbons 1 and 2 (PubMed:24239699, PubMed:27921136). No monoxy
CC       or dioxy-intermediates have been reported to be released to the broth,
CC       so these three early oxidative reactions may be coupled together
CC       (PubMed:24239699). Eremofortin B is further oxidized by another P450
CC       monooxygenase, that introduces a second epoxide between carbons 7 and
CC       11 prior to acetylation to eremofortin A by the acetyltransferase ORF8
CC       (PubMed:16345540, PubMed:24239699, PubMed:27921136). The second
CC       epoxidation may be performed by a second P450 monooxygenase
CC       (PubMed:24239699). After the acetylation step, eremofortin A is
CC       converted to eremofortin C and then to PR-toxin (PubMed:24239699).
CC       First the conversion of eremofortin A to eremofortin C proceeds by
CC       oxidation of the side chain of the molecule at C-12 and is catalyzed by
CC       the short-chain oxidoreductase prx1 (PubMed:16345540, PubMed:24239699).
CC       The cytochrome P450 monooxygenase ORF6 is probably also involved in
CC       this step (PubMed:27921136). The primary alcohol formed at C-12 is
CC       finally oxidized by the short-chain alcohol dehydrogenase prx4 that
CC       forms PR-toxin (PubMed:16345540, PubMed:24239699).
CC       {ECO:0000269|PubMed:15186158, ECO:0000269|PubMed:16345540,
CC       ECO:0000269|PubMed:24239699, ECO:0000269|PubMed:26274339,
CC       ECO:0000269|PubMed:27921136, ECO:0000269|PubMed:8440737}.
CC   -!- PATHWAY: Sesquiterpene biosynthesis. {ECO:0000305|PubMed:24239699,
CC       ECO:0000305|PubMed:27921136}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
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DR   EMBL; HG792016; CDM31320.1; -; Genomic_DNA.
DR   AlphaFoldDB; W6Q4S2; -.
DR   SMR; W6Q4S2; -.
DR   EnsemblFungi; CDM31320; CDM31320; PROQFM164_S02g001470.
DR   OrthoDB; 1411163at2759; -.
DR   Proteomes; UP000030686; Unassembled WGS sequence.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
PE   3: Inferred from homology;
KW   Membrane; Transmembrane; Transmembrane helix.
FT   CHAIN           1..186
FT                   /note="PR-toxin biosynthesis cluster protein 7"
FT                   /id="PRO_0000451231"
FT   TRANSMEM        24..43
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   186 AA;  20808 MW;  30624ED8C79DF1E7 CRC64;
     MEPQTKDPDP LPRLVHIGEI QFNLGEVTTG GVTPRGTFIF CPITGGHFTT VFPLPDGFGI
     HSEAIEGLRA EVLPGGGDYP LIHNNELAEL NVSVVAKGLN NDHIFRITSF GICEWNKLIF
     DMMGQTAAAR STEMGEINAW QVFRINTDSP EYAWLNWACI IGQERLIYED SRMAKTHMKL
     FQFLVK