ID   PRX7_PENRW              Reviewed;         282 AA.
AC   B6H061;
DT   07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT   16-DEC-2008, sequence version 1.
DT   03-AUG-2022, entry version 65.
DE   RecName: Full=Short-chain dehydrogenase/reductase prx7 {ECO:0000303|PubMed:24239699};
DE            EC=1.1.99.- {ECO:0000305|PubMed:24239699};
DE   AltName: Full=PR-toxin biosynthesis cluster protein 7 {ECO:0000303|PubMed:24239699};
GN   Name=prx7 {ECO:0000303|PubMed:24239699};
GN   ORFNames=Pc12g06280, PCH_Pc12g06280;
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: Short-chain dehydrogenase/reductase; part of the gene cluster
CC       that mediates the biosynthesis of PR-toxin, a bicyclic sesquiterpene
CC       belonging to the eremophilane class and acting as a mycotoxin
CC       (PubMed:24239699). 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:24239699). Following the formation of aristolochene, the non-
CC       oxygenated aristolochene is converted to the trioxygenated intermediate
CC       eremofortin B, via 7-epi-neopetasone (PubMed:24239699). This conversion
CC       appears to involve three enzymes, a hydroxysterol oxidase-like enzyme,
CC       the 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 prx9 that introduces the
CC       epoxide at the double bond between carbons 1 and 2 (PubMed:24239699)
CC       (By similarity). No monoxy or dioxy-intermediates have been reported to
CC       be released to the broth, so these three early oxidative reactions may
CC       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 prx11 (By similarity). The second epoxidation
CC       may be performed by a second P450 monooxygenase (PubMed:24239699).
CC       After the acetylation step, eremofortin A is converted to eremofortin C
CC       and then to PR-toxin (PubMed:24239699). First the conversion of
CC       eremofortin A to eremofortin C proceeds by oxidation of the side chain
CC       of the molecule at C-12 and is catalyzed by the short-chain
CC       oxidoreductase prx1 (PubMed:24239699). The cytochrome P450
CC       monooxygenase prx8 also plays a role in this step (By similarity). The
CC       primary alcohol formed at C-12 is finally oxidized by the short-chain
CC       alcohol dehydrogenase prx4 that forms PR-toxin (PubMed:24239699).
CC       {ECO:0000250|UniProtKB:W6Q3Z9, ECO:0000250|UniProtKB:W6QB15,
CC       ECO:0000250|UniProtKB:W6QP10, ECO:0000269|PubMed:24239699}.
CC   -!- PATHWAY: Sesquiterpene biosynthesis. {ECO:0000305|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}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; AM920427; CAP80255.1; -; Genomic_DNA.
DR   RefSeq; XP_002557471.1; XM_002557425.1.
DR   AlphaFoldDB; B6H061; -.
DR   SMR; B6H061; -.
DR   EnsemblFungi; CAP80255; CAP80255; PCH_Pc12g06280.
DR   GeneID; 8313014; -.
DR   KEGG; pcs:Pc12g06280; -.
DR   VEuPathDB; FungiDB:PCH_Pc12g06280; -.
DR   eggNOG; KOG4169; Eukaryota.
DR   HOGENOM; CLU_010194_13_0_1; -.
DR   OMA; VIERTNF; -.
DR   OrthoDB; 1053465at2759; -.
DR   BioCyc; PCHR:PC12G06280-MON; -.
DR   Proteomes; UP000000724; Contig Pc00c12.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR   InterPro; IPR002347; SDR_fam.
DR   Pfam; PF00106; adh_short; 1.
DR   PRINTS; PR00081; GDHRDH.
DR   PRINTS; PR00080; SDRFAMILY.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   PROSITE; PS00061; ADH_SHORT; 1.
PE   2: Evidence at transcript level;
KW   NAD; Oxidoreductase; Reference proteome.
FT   CHAIN           1..282
FT                   /note="Short-chain dehydrogenase/reductase prx7"
FT                   /id="PRO_0000451219"
FT   ACT_SITE        150
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT   BINDING         26..29
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         82..87
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         192..196
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
SQ   SEQUENCE   282 AA;  30891 MW;  1EE17BC3EA8F785F CRC64;
     MGLAVAKALS LQKDWEIYIL DINSERGAET AKELPRTTFH YANVTKYSDL AAAFQSMFQQ
     HGKLDFVFAN AGVIERTNFY STPQAENDMD VCPPPEPDLP SIDADLKGVV FTAYLAQHYF
     RHSPHRGHGG SLVMTASCGG LYPSFYSPLY SAAKFGVVGF MRSISQHFHA SGIRVNAICP
     GIVRTNLVDS AGWDSFPPGR FIEVETIARL VLQLVDGGEP AGRGLTDTTG RHLPLEELYG
     VAVEISDSGF YFRDQHTFCD EGMREVMDAT VVENQVGAVL NG