PRX2_PENRW
ID PRX2_PENRW Reviewed; 342 AA.
AC B6H063;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 1.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=Aristolochene synthase prx2 {ECO:0000303|PubMed:24239699};
DE Short=AS {ECO:0000303|PubMed:24239699};
DE EC=4.2.3.9 {ECO:0000305|PubMed:24239699};
DE AltName: Full=PR-toxin biosynthesis protein 2 {ECO:0000303|PubMed:24239699};
DE AltName: Full=Sesquiterpene cyclase prx2 {ECO:0000303|PubMed:24239699};
GN Name=pxr2 {ECO:0000303|PubMed:24239699}; ORFNames=Pc12g06310;
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, AND INDUCTION.
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: Aristolochene synthase; 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, the conversion of eremofortin A to
CC eremofortin C and then to PR-toxin requires only two enzymes
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 -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate = (+)-aristolochene +
CC diphosphate; Xref=Rhea:RHEA:19825, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:43445, ChEBI:CHEBI:175763; EC=4.2.3.9;
CC Evidence={ECO:0000250|UniProtKB:Q03471};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9UR08};
CC Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q9UR08};
CC -!- PATHWAY: Sesquiterpene biosynthesis; aristolochene biosynthesis;
CC aristolochene from farnesyl diphosphate: step 1/1.
CC {ECO:0000250|UniProtKB:Q03471}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q9UR08}.
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 terpene synthase family. {ECO:0000305}.
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DR EMBL; AM920427; CAP80258.1; -; Genomic_DNA.
DR RefSeq; XP_002557473.1; XM_002557427.1.
DR AlphaFoldDB; B6H063; -.
DR SMR; B6H063; -.
DR STRING; 1108849.XP_002557473.1; -.
DR EnsemblFungi; CAP80258; CAP80258; PCH_Pc12g06310.
DR GeneID; 8313017; -.
DR KEGG; pcs:Pc12g06310; -.
DR VEuPathDB; FungiDB:PCH_Pc12g06310; -.
DR eggNOG; ENOG502SK06; Eukaryota.
DR HOGENOM; CLU_057570_1_0_1; -.
DR OMA; IYCPRYH; -.
DR OrthoDB; 1143139at2759; -.
DR BioCyc; PCHR:PC12G06310-MON; -.
DR UniPathway; UPA00177; UER00582.
DR Proteomes; UP000000724; Contig Pc00c12.
DR GO; GO:0045483; F:aristolochene synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR SUPFAM; SSF48576; SSF48576; 1.
PE 2: Evidence at transcript level;
KW Lyase; Magnesium; Metal-binding; Reference proteome.
FT CHAIN 1..342
FT /note="Aristolochene synthase prx2"
FT /id="PRO_0000438191"
FT BINDING 115
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 115
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 115
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q03471"
FT BINDING 200
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 244
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 244
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q03471"
FT BINDING 248
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 251
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 252
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT SITE 92
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q03471"
FT SITE 112
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q03471"
FT SITE 178
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q03471"
FT SITE 334
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q03471"
SQ SEQUENCE 342 AA; 39153 MW; C1BAC1D02BFEAC53 CRC64;
MATLTETITS LAQPFVHLED TINSPPVKET IRPRNDTTIT PPPTQWSYLC HPRVKEVQDE
VDGYFLENWK FPSFKAVRTF LGAKFSEVTC LYFPLALDDR IHFACRLLTV LFLIDDVLEH
MSFADGEAYN NRLIPISRGD VLPDRTKPEE FILYDLWESM RAHDAELANE VLEPTFVFMR
AQTDRARLTI HELGHYLEYR EKDVGKALLS ALMRFSMGLR FSADELQGMK ALEANCAKQL
SVVNDIYSYD KEEEASRTGH KEGAFLCSAV KVLAEESKLG IPATKRVLWS MTREWETVHD
EIVAEKIASP DGCSEAAKAY MKGLEYQMSG NEQWSKTTRR YN
