PRX3_PENRW
ID PRX3_PENRW Reviewed; 512 AA.
AC B6H064;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 1.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=FAD-dependent monooxygenase prx3 {ECO:0000303|PubMed:24239699};
DE EC=1.-.-.- {ECO:0000305|PubMed:24239699};
DE AltName: Full=PR-toxin biosynthesis cluster protein 3 {ECO:0000303|PubMed:24239699};
DE Flags: Precursor;
GN Name=prx3 {ECO:0000303|PubMed:24239699};
GN ORFNames=Pc12g06320, PCH_Pc12g06320;
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: FAD-dependent monooxygenase; part of the gene cluster that
CC 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 oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AM920427; CAP80259.1; -; Genomic_DNA.
DR RefSeq; XP_002557474.1; XM_002557428.1.
DR AlphaFoldDB; B6H064; -.
DR SMR; B6H064; -.
DR STRING; 1108849.XP_002557474.1; -.
DR EnsemblFungi; CAP80259; CAP80259; PCH_Pc12g06320.
DR GeneID; 8313018; -.
DR KEGG; pcs:Pc12g06320; -.
DR VEuPathDB; FungiDB:PCH_Pc12g06320; -.
DR eggNOG; KOG1231; Eukaryota.
DR HOGENOM; CLU_018354_1_2_1; -.
DR OMA; ENDTNPV; -.
DR OrthoDB; 733611at2759; -.
DR BioCyc; PCHR:PC12G06320-MON; -.
DR Proteomes; UP000000724; Contig Pc00c12.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 2: Evidence at transcript level;
KW FAD; Flavoprotein; Glycoprotein; Oxidoreductase; Reference proteome;
KW Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..512
FT /note="FAD-dependent monooxygenase prx3"
FT /id="PRO_5002843371"
FT DOMAIN 63..235
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 281
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 307
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 329
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 361
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 477
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 512 AA; 54714 MW; A3618A6238E2D2D8 CRC64;
MLSLGAFLAL SLSFHLSQGV VASVLHRRAN ACKKLSRSYP NSTIHPGSSV FAEDVIEPWS
QTCQTTPTCV FAPASAEEVA GGLAILRKAD QTFAVRTQGH MPIPGAADIS NGVLMVTTSL
NSVQYADDSK SVVQIGAGNR WLDVYKVLAK DSLAVAGGRF GQVGVSGLLL GGGISYFNSD
HGWGANSVVN YEVVLANGTV CAANAQQNSD LYWALKGGAF NFGIVTRFDL ATFSVPYMWG
GSAYYDASAL DPLVNAYASY AVASGGSSDP AAHSDPSILY NVTTGEVSGY SIYMHRGDDP
APAALKNFTD IPSTFQDFRV GKTILGHEND TNPVNFGVGN RRQLFSSTAL ASSAEAVYLV
NQTFFDVIAA NPQIKTTTDL SVTNTYQLFT PGMIRAAETS GGDPIGLYDP LGNGVLAVLY
GGNWADAKDD ETIYKFFQDM IDELDNRAKK VGLYYDFVYL NDAAPTQTKD IFQKFSNGTA
LPKLREIAES YDPDQVFQTL TPGGFKFINS PA
