PRX9_PENRW
ID PRX9_PENRW Reviewed; 579 AA.
AC B6H067;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 1.
DT 03-AUG-2022, entry version 61.
DE RecName: Full=Cytochrome P450 monooxygenase prx9 {ECO:0000303|PubMed:24239699};
DE EC=1.-.-.- {ECO:0000305|PubMed:24239699};
DE AltName: Full=PR-toxin biosynthesis cluster protein 9 {ECO:0000303|PubMed:24239699};
GN Name=prx9 {ECO:0000303|PubMed:24239699};
GN ORFNames=Pc12g06350, PCH_Pc12g06350;
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: Cytochrome P450 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 -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Sesquiterpene biosynthesis. {ECO:0000305|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 cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AM920427; CAP80262.1; -; Genomic_DNA.
DR RefSeq; XP_002557477.1; XM_002557431.1.
DR AlphaFoldDB; B6H067; -.
DR SMR; B6H067; -.
DR EnsemblFungi; CAP80262; CAP80262; PCH_Pc12g06350.
DR GeneID; 8313021; -.
DR KEGG; pcs:Pc12g06350; -.
DR VEuPathDB; FungiDB:PCH_Pc12g06350; -.
DR eggNOG; KOG0157; Eukaryota.
DR HOGENOM; CLU_001570_25_2_1; -.
DR OMA; YGPNVAT; -.
DR OrthoDB; 786853at2759; -.
DR BioCyc; PCHR:PC12G06350-MON; -.
DR Proteomes; UP000000724; Contig Pc00c12.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 2: Evidence at transcript level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..579
FT /note="Cytochrome P450 monooxygenase prx9"
FT /id="PRO_0000451225"
FT TRANSMEM 6..25
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 512
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 194
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 390
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 579 AA; 65534 MW; BFBAF0E3F38F5496 CRC64;
MDASKLPLGS FVGTTLLLFI LYKLVKLAYY VGQAKNTGLP YTIVPVLETE FLGKLLTPLI
RPLFTSRLSR GKGWPRWIRF SILDWAWEEK RRVHEELGDV FLVVSSEGLI CYTADADMSW
DVMNRRNEFL KPRDKYKVLE PYGPNVATTE GKAYNFHVRI TAPPFNDGSG ANDLVWNEAS
DQARALMESW SQENTTRDLS LDINRLTLAV IAYTGFGKRL DFKTEVSDLR NKIPPGYKMS
LHHALHLVTT FMVKILLIPK WIMKMTSMKE IAVAHGELEK YMREMIRTET ANLSKDSEYQ
SADAKGNLLT SVLRASAFEA KAAGRKQAFS EDEVLGNLFL YLLAGYETTA NAMTYGFITL
ALRQDLQDRI IQEVDGVYAE AAAEGRTSLN YTDDFEKFQY TYGFMYEVFR LYPGVCIITK
MVPKDTTITV YPENNSPQQH VLPAECRVYL NVNAVHYHER YWPDPWALKP DRWMGTIGAT
PNARSNKKVV AGDKSRQVRG TLMTFSGGAR ACLGRKFTQS EYISALATVL REYRIVLGEG
MDAKVVKQEI DHLAAGTVTL APLKYVKLAL KKRTDVKTG
