ID   PRX10_PENRW             Reviewed;         166 AA.
AC   B6H068;
DT   07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT   16-DEC-2008, sequence version 1.
DT   03-AUG-2022, entry version 30.
DE   RecName: Full=PR-toxin biosynthesis cluster protein 10 {ECO:0000303|PubMed:24239699};
GN   Name=prx10 {ECO:0000303|PubMed:24239699};
GN   ORFNames=Pc12g06360, PCH_Pc12g06360;
OS   Penicillium rubens (strain ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin
OS   54-1255) (Penicillium chrysogenum).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium;
OC   Penicillium chrysogenum species complex.
OX   NCBI_TaxID=500485;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin 54-1255;
RX   PubMed=18820685; DOI=10.1038/nbt.1498;
RA   van den Berg M.A., Albang R., Albermann K., Badger J.H., Daran J.-M.,
RA   Driessen A.J.M., Garcia-Estrada C., Fedorova N.D., Harris D.M.,
RA   Heijne W.H.M., Joardar V.S., Kiel J.A.K.W., Kovalchuk A., Martin J.F.,
RA   Nierman W.C., Nijland J.G., Pronk J.T., Roubos J.A., van der Klei I.J.,
RA   van Peij N.N.M.E., Veenhuis M., von Doehren H., Wagner C., Wortman J.R.,
RA   Bovenberg R.A.L.;
RT   "Genome sequencing and analysis of the filamentous fungus Penicillium
RT   chrysogenum.";
RL   Nat. Biotechnol. 26:1161-1168(2008).
RN   [2]
RP   FUNCTION, INDUCTION, AND PATHWAY.
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).
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). The first step of the
CC       pathway is catalyzed by the aristolochene synthase which performs the
CC       cyclization of trans,trans-farnesyl diphosphate (FPP) to the bicyclic
CC       sesquiterpene aristolochene (PubMed:24239699). Following the formation
CC       of aristolochene, the non-oxygenated aristolochene is converted to the
CC       trioxygenated intermediate eremofortin B, via 7-epi-neopetasone
CC       (PubMed:24239699). This conversion appears to involve three enzymes, a
CC       hydroxysterol oxidase-like enzyme, the quinone-oxidase prx3 that forms
CC       the quinone-type-structure in the bicyclic nucleus of aristolochene
CC       with the C8-oxo group and the C-3 hydroxyl group, and the P450
CC       monooxygenase prx9 that introduces the epoxide at the double bond
CC       between carbons 1 and 2 (PubMed:24239699) (By similarity). No monoxy or
CC       dioxy-intermediates have been reported to be released to the broth, so
CC       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 prx11
CC       (By similarity). 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:24239699).
CC       The cytochrome P450 monooxygenase prx8 also plays a role in this step
CC       (By similarity). The primary alcohol formed at C-12 is finally oxidized
CC       by the short-chain alcohol dehydrogenase prx4 that forms PR-toxin
CC       (PubMed:24239699). {ECO:0000250|UniProtKB:W6Q3Z9,
CC       ECO:0000250|UniProtKB:W6QB15, ECO:0000250|UniProtKB:W6QP10,
CC       ECO:0000269|PubMed:24239699}.
CC   -!- INDUCTION: Expression and the subsequent production of PR-toxin take
CC       place under static culture conditions (oxygen limited), whereas no
CC       expression of the PR-toxin genes occurs under the strongly aerated
CC       conditions required for optimal penicillin production
CC       (PubMed:24239699). There is a negative control of the transcription of
CC       the PR-toxin genes by the penicillin biosynthesis gene product(s), or
CC       by a regulatory peptide encoded by a small ORF inside the penicillin
CC       gene cluster (PubMed:24239699). {ECO:0000269|PubMed:24239699}.
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DR   EMBL; AM920427; CAP80263.1; -; Genomic_DNA.
DR   RefSeq; XP_002557478.1; XM_002557432.1.
DR   AlphaFoldDB; B6H068; -.
DR   EnsemblFungi; CAP80263; CAP80263; PCH_Pc12g06360.
DR   GeneID; 8313022; -.
DR   KEGG; pcs:Pc12g06360; -.
DR   VEuPathDB; FungiDB:PCH_Pc12g06360; -.
DR   HOGENOM; CLU_1603293_0_0_1; -.
DR   OrthoDB; 1717476at2759; -.
DR   Proteomes; UP000000724; Contig Pc00c12.
PE   2: Evidence at transcript level;
KW   Reference proteome.
FT   CHAIN           1..166
FT                   /note="PR-toxin biosynthesis cluster protein 10"
FT                   /id="PRO_0000451232"
SQ   SEQUENCE   166 AA;  18843 MW;  AB6F98AF545F19A3 CRC64;
     MIPLRCSSAY SLLIEYCATI RDPCEETYTS RGDHNLSISI SLFDQKLEQF HVSLSHATVL
     VNQSLLPNDA CPIQPGILRA ISVDAKNLPC VDFPHLCRAR GGCLAHHIEY EFVPFAYTER
     GDTEYMIVVE TLGDDADIQF RKFIVMYQRI IAATWKHLCP QTFDCL