PRX4_PENRW
ID PRX4_PENRW Reviewed; 329 AA.
AC B6H065;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Short-chain dehydrogenase/reductase prx4 {ECO:0000303|PubMed:24239699};
DE EC=1.1.99.- {ECO:0000305|PubMed:24239699};
DE AltName: Full=PR-toxin biosynthesis cluster protein 4 {ECO:0000303|PubMed:24239699};
DE Flags: Precursor;
GN Name=prx4 {ECO:0000303|PubMed:24239699};
GN ORFNames=Pc12g06330, PCH_Pc12g06330;
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:0000269|PubMed:24239699}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
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; CAP80260.1; -; Genomic_DNA.
DR RefSeq; XP_002557475.1; XM_002557429.1.
DR AlphaFoldDB; B6H065; -.
DR SMR; B6H065; -.
DR STRING; 1108849.XP_002557475.1; -.
DR EnsemblFungi; CAP80260; CAP80260; PCH_Pc12g06330.
DR GeneID; 8313019; -.
DR KEGG; pcs:Pc12g06330; -.
DR VEuPathDB; FungiDB:PCH_Pc12g06330; -.
DR eggNOG; KOG0725; Eukaryota.
DR HOGENOM; CLU_010194_13_1_1; -.
DR OMA; TGYAPEQ; -.
DR OrthoDB; 1053465at2759; -.
DR BioCyc; PCHR:PC12G06330-MON; -.
DR Proteomes; UP000000724; Contig Pc00c12.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 2: Evidence at transcript level;
KW Glycoprotein; Membrane; NAD; Oxidoreductase; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..329
FT /note="Short-chain dehydrogenase/reductase prx4"
FT /id="PRO_5002845320"
FT TRANSMEM 238..258
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 194
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 52..60
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 79..80
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 107..109
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 194..198
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 232..234
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 329 AA; 35582 MW; 055D5E2B85A2CF36 CRC64;
MIPRWQPASI ALLLHLDTLR CHHVSVRPPR ATMTSLSIKE EDIPRLDGKV VVISGGASGI
GLAAANIFAR AGAKIFLFDR NPPDSGEAPE NSTFIKADVT SWAELKAAFA QAGHVDIAVA
NAGVSEEQPY FEDTFDEQGE LKEPGFAVVD VNFKGTVMFT KLAVSYMRKQ GKGGSVVITA
SATGYAPEQN LPVYSAIKSG LVGLVRSLRS TLPRFDISIN AVAPAATITK LLPMDIAGPL
MAAGLPVSSA HMVGLAVVYS AVARQPRMVE TYGKENMLDL ESKWNGRTIL TLGEHYTELE
EKLADLRPVW FGWRNTDLTK KQQATADFR
