ID   PRX11_PENRF             Reviewed;         471 AA.
AC   W6QP10;
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=Eremophilane O-acetyltransferase ORF8 {ECO:0000303|PubMed:27921136};
DE            EC=2.3.1.- {ECO:0000305|PubMed:27921136};
DE   AltName: Full=PR-toxin biosynthesis cluster protein 8 {ECO:0000303|PubMed:27921136};
GN   Name=ORF8 {ECO:0000303|PubMed:27921136}; ORFNames=PROQFM164_S02g001472;
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, DISRUPTION PHENOTYPE, 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: O-acetyltransferase; part of the gene cluster that mediates
CC       the biosynthesis of PR-toxin, a bicyclic sesquiterpene belonging to the
CC       eremophilane class and acting as a mycotoxin (PubMed:24239699,
CC       PubMed:27921136). The first step of the pathway is catalyzed by the
CC       aristolochene synthase which performs the cyclization of trans,trans-
CC       farnesyl diphosphate (FPP) to the bicyclic sesquiterpene aristolochene
CC       (PubMed:8440737, PubMed:15186158, PubMed:24239699). Following the
CC       formation of aristolochene, the non-oxygenated aristolochene is
CC       converted to the trioxygenated intermediate eremofortin B, via 7-epi-
CC       neopetasone (PubMed:24239699, PubMed:26274339). This conversion appears
CC       to involve three enzymes, a hydroxysterol oxidase-like enzyme, the
CC       quinone-oxidase prx3 that forms the quinone-type-structure in the
CC       bicyclic nucleus of aristolochene with the C8-oxo group and the C-3
CC       hydroxyl group, and the P450 monooxygenase ORF6 that introduces the
CC       epoxide at the double bond between carbons 1 and 2 (PubMed:24239699,
CC       PubMed:27921136). No monoxy or dioxy-intermediates have been reported
CC       to be released to the broth, so these three early oxidative reactions
CC       may be coupled together (PubMed:24239699). Eremofortin B is further
CC       oxidized by another P450 monooxygenase, that introduces a second
CC       epoxide between carbons 7 and 11 prior to acetylation to eremofortin A
CC       by the acetyltransferase ORF8 (PubMed:16345540, PubMed:24239699,
CC       PubMed:27921136). The second epoxidation may be performed by a second
CC       P450 monooxygenase (PubMed:24239699). After the acetylation step,
CC       eremofortin A is converted to eremofortin C and then to PR-toxin
CC       (PubMed:24239699). First the conversion of eremofortin A to eremofortin
CC       C proceeds by oxidation of the side chain of the molecule at C-12 and
CC       is catalyzed by the short-chain oxidoreductase prx1 (PubMed:16345540,
CC       PubMed:24239699). The cytochrome P450 monooxygenase ORF6 is probably
CC       also involved in this step (PubMed:27921136). The primary alcohol
CC       formed at C-12 is finally oxidized by the short-chain alcohol
CC       dehydrogenase prx4 that forms PR-toxin (PubMed:16345540,
CC       PubMed:24239699). {ECO:0000269|PubMed:15186158,
CC       ECO:0000269|PubMed:16345540, ECO:0000269|PubMed:24239699,
CC       ECO:0000269|PubMed:26274339, ECO:0000269|PubMed:27921136,
CC       ECO:0000269|PubMed:8440737}.
CC   -!- PATHWAY: Sesquiterpene biosynthesis. {ECO:0000269|PubMed:27921136,
CC       ECO:0000305|PubMed:24239699}.
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q4WZ64}.
CC   -!- DISRUPTION PHENOTYPE: Impairs the production of PR-toxin as well as of
CC       the intermediate eremofortin A, but accumulates eremofortin B.
CC       {ECO:0000269|PubMed:27921136}.
CC   -!- SIMILARITY: Belongs to the fumigaclavine B O-acetyltransferase family.
CC       {ECO:0000305}.
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DR   EMBL; HG792016; CDM31322.1; -; Genomic_DNA.
DR   AlphaFoldDB; W6QP10; -.
DR   SMR; W6QP10; -.
DR   EnsemblFungi; CDM31322; CDM31322; PROQFM164_S02g001472.
DR   OrthoDB; 1130893at2759; -.
DR   Proteomes; UP000030686; Unassembled WGS sequence.
DR   GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.30.559.10; -; 2.
DR   InterPro; IPR023213; CAT-like_dom_sf.
PE   3: Inferred from homology;
KW   Acyltransferase; Transferase.
FT   CHAIN           1..471
FT                   /note="Eremophilane O-acetyltransferase ORF8"
FT                   /id="PRO_0000451229"
SQ   SEQUENCE   471 AA;  53130 MW;  8D7F587FACBB38F9 CRC64;
     MYELQQHRKF SALDEMLPAF YYCYLLCFPV SSDNRASTSE LLQTSLSSLA EERPYLTGTV
     RRDMESSVRK GHLILDIPNP FEDLRIVFND LTGPKSQWKE TYQDLKDTGM PPHKLDANLL
     APLTAGIGET RKVMSVQANF IHGGLLIAFC FHHNFVDAYG AGRIIARFSD HCNGTVDLKN
     SADPEGDGTD SRGIADLLDV ELLKKQYKFE DLESDPNLWR LNCLEFRGVN DFRWPDFIPA
     LLPVRKPPVI SSMFSFSSDA LAEIKAMAQP NQSGAWVSTN DALVAFLWRH TMRARFPSSR
     TESEPPNRKS NVVVALDGRK DLSISPTYIG NCLFHCFTDL PINMVGSEST HLGDIAIKVR
     QTITAARNKT LLKAVVGLAA THPDCQTIKY ANDNLGPDLY VTSWIDLPFY KLEWGPLGKT
     EFFRIPDRQF ESLCCILPPK DGVVQLITSM EEDHSKRLRS DAEFTRFATY R