ROQD_PENRW
ID ROQD_PENRW Reviewed; 422 AA.
AC B6HJU1;
DT 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=Roquefortine prenyltransferase roqD {ECO:0000303|PubMed:22118684};
DE EC=2.5.1.- {ECO:0000269|PubMed:22118684, ECO:0000269|PubMed:23776469, ECO:0000269|PubMed:24225953};
DE AltName: Full=Roquefortien/meleagrin synthesis protein D {ECO:0000305};
GN Name=roqD {ECO:0000303|PubMed:23776469};
GN Synonyms=rpt {ECO:0000303|PubMed:22118684}; ORFNames=Pc21g15430;
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 DISRUPTION PHENOTYPE.
RX PubMed=22118684; DOI=10.1016/j.chembiol.2011.08.012;
RA Garcia-Estrada C., Ullan R.V., Albillos S.M., Fernandez-Bodega M.A.,
RA Durek P., von Doehren H., Martin J.F.;
RT "A single cluster of coregulated genes encodes the biosynthesis of the
RT mycotoxins roquefortine C and meleagrin in Penicillium chrysogenum.";
RL Chem. Biol. 18:1499-1512(2011).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24225953; DOI=10.1074/jbc.m113.512665;
RA Ries M.I., Ali H., Lankhorst P.P., Hankemeier T., Bovenberg R.A.,
RA Driessen A.J., Vreeken R.J.;
RT "Novel key metabolites reveal further branching of the
RT roquefortine/meleagrin biosynthetic pathway.";
RL J. Biol. Chem. 288:37289-37295(2013).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23776469; DOI=10.1371/journal.pone.0065328;
RA Ali H., Ries M.I., Nijland J.G., Lankhorst P.P., Hankemeier T.,
RA Bovenberg R.A., Vreeken R.J., Driessen A.J.;
RT "A branched biosynthetic pathway is involved in production of roquefortine
RT and related compounds in Penicillium chrysogenum.";
RL PLoS ONE 8:E65328-E65328(2013).
RN [5]
RP BIOTECHNOLOGY.
RX PubMed=26692349; DOI=10.1016/j.bmc.2015.11.038;
RA Mady M.S., Mohyeldin M.M., Ebrahim H.Y., Elsayed H.E., Houssen W.E.,
RA Haggag E.G., Soliman R.F., El Sayed K.A.;
RT "The indole alkaloid meleagrin, from the olive tree endophytic fungus
RT Penicillium chrysogenum, as a novel lead for the control of c-Met-dependent
RT breast cancer proliferation, migration and invasion.";
RL Bioorg. Med. Chem. 24:113-122(2016).
CC -!- FUNCTION: Roquefortine prenyltransferase; part of the gene cluster that
CC mediates the biosynthesis of the mycotoxins roquefortine C and
CC meleagrin (PubMed:22118684, PubMed:23776469). The first stage is
CC catalyzed by the dipeptide synthase roqA which condenses histidine and
CC tryptophan to produce histidyltryptophanyldiketopiperazine (HTD)
CC (PubMed:22118684, PubMed:23776469). HTD is then converted to
CC roquefortine C through two possible pathways (PubMed:23776469). In the
CC first pathway, prenyltransferase roqD transforms HTD to the
CC intermediate roquefortine D, which is in turn converted to roquefortine
CC C by the cytochrome P450 monooxygenase roqR (PubMed:23776469). In the
CC second pathway, HTD is first converted to the intermediate
CC dehydrohistidyltryptophanyldi-ketopiperazine (DHTD) by roqR which is
CC then prenylated by roqD to form roquefortine C (PubMed:23776469).
CC Roquefortine C can be further transformed to meleagrin via three more
CC reactions including oxydation to glandicolin A by roqM, which is
CC further reduced to glandicoline B by roqO (PubMed:23776469). Finally,
CC glandicoline B is converted to meleagrin by the glandicoline B O-
CC methyltransferase roqN (PubMed:22118684, PubMed:23776469). More studies
CC identified further branching and additional metabolites produced by the
CC roquefortine/meleagrin cluster, including roquefortine F, roquefortine
CC L, roquefortine M, roquefortine N and neoxaline (PubMed:24225953).
CC {ECO:0000269|PubMed:22118684, ECO:0000269|PubMed:23776469,
CC ECO:0000269|PubMed:24225953}.
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:22118684,
CC ECO:0000269|PubMed:23776469, ECO:0000269|PubMed:24225953}.
CC -!- INDUCTION: Expression is decreased in presence of phenylacetic acid
CC (PAA) (PubMed:23776469). {ECO:0000269|PubMed:23776469}.
CC -!- DISRUPTION PHENOTYPE: Leads to a drastic reduction of both roquefortine
CC C and meleagrin synthesis (PubMed:22118684). Accumulates high lebels of
CC HTD (PubMed:23776469). {ECO:0000269|PubMed:22118684,
CC ECO:0000269|PubMed:23776469}.
CC -!- BIOTECHNOLOGY: The indole alkaloid meleagrin was shown to be a good
CC candidate to control c-Met-dependent breast cancer proliferation,
CC migration and invasion (PubMed:26692349).
CC {ECO:0000269|PubMed:26692349}.
CC -!- SIMILARITY: Belongs to the tryptophan dimethylallyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AM920436; CAP96440.1; -; Genomic_DNA.
DR RefSeq; XP_002568553.1; XM_002568507.1.
DR AlphaFoldDB; B6HJU1; -.
DR SMR; B6HJU1; -.
DR STRING; 1108849.XP_002568553.1; -.
DR MEROPS; M77.003; -.
DR EnsemblFungi; CAP96440; CAP96440; PCH_Pc21g15430.
DR GeneID; 8315544; -.
DR KEGG; pcs:Pc21g15430; -.
DR VEuPathDB; FungiDB:PCH_Pc21g15430; -.
DR eggNOG; ENOG502S2XP; Eukaryota.
DR HOGENOM; CLU_037431_0_0_1; -.
DR OMA; CFSAIRK; -.
DR OrthoDB; 1531660at2759; -.
DR BioCyc; PCHR:PC21G15430-MON; -.
DR Proteomes; UP000000724; Contig Pc00c21.
DR GO; GO:0004659; F:prenyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0009820; P:alkaloid metabolic process; IEA:InterPro.
DR GO; GO:0044249; P:cellular biosynthetic process; IEA:UniProt.
DR GO; GO:1901576; P:organic substance biosynthetic process; IEA:UniProt.
DR CDD; cd13929; PT-DMATS_CymD; 1.
DR InterPro; IPR033964; Aro_prenylTrfase.
DR InterPro; IPR017795; Aro_prenylTrfase_DMATS.
DR InterPro; IPR012148; DMATS-type_fun.
DR PANTHER; PTHR40627; PTHR40627; 1.
DR Pfam; PF11991; Trp_DMAT; 1.
DR PIRSF; PIRSF000509; Trp_DMAT; 1.
DR SFLD; SFLDS00036; Aromatic_Prenyltransferase; 1.
DR TIGRFAMs; TIGR03429; arom_pren_DMATS; 1.
PE 1: Evidence at protein level;
KW Prenyltransferase; Reference proteome; Transferase.
FT CHAIN 1..422
FT /note="Roquefortine prenyltransferase roqD"
FT /id="PRO_0000436345"
FT BINDING 100
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 113
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 200
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 202
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 204
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 268
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 270
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 353
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 416
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 420
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
SQ SEQUENCE 422 AA; 47326 MW; B19410151950D4D0 CRC64;
MTVSSTVQPL KACVPEATEA ADMPHHTLSK SMTFANLDQY QYWHAVGPML GRMLSNGSYS
IHKQYEYLCL FAHVIIPKLG PFPGGRDIYK CLLGGTGSVE LSQNVQKLGL TARVAFEPTS
YIASTGVDPL NRHTVHATLV ELRAIGSASI DMELHQMLVN ELTLTDREER LMSPEAISGT
AWKTQILLAL DLGQTGITIK EYFYPALKAS VTGQSVAKLC FSAIRKVDKQ GRFEPASKAI
ETYMKTQSQT DLYFLSCDLV DPAATRIKLY LMELDMRLAK VEEHWTMGGK LNDEETLLGL
KMLQELWVEF GIIEGMRNEP ERPSLPGDPD TIVPFIMNYE MSPGEALPKP KFYFPLVGIP
ELKIANVLTA FFERYGMPEQ AAVYRNNLQT PSKDLVIATD HQAWLSFSYT KKKGPYLTMY
YH
