ROQR_PENRW
ID ROQR_PENRW Reviewed; 511 AA.
AC B6HJU5;
DT 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Cytochrome P450 monooxygenase roqR {ECO:0000305};
DE EC=1.-.-.- {ECO:0000269|PubMed:22118684, ECO:0000269|PubMed:23776469, ECO:0000269|PubMed:24225953};
DE AltName: Full=Roquefortine/meleagrin synthesis protein R {ECO:0000303|PubMed:23776469};
DE Flags: Precursor;
GN Name=roqR {ECO:0000303|PubMed:23776469}; ORFNames=Pc21g15470;
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: Cytochrome P450 monooxygenase; 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 -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:22118684,
CC ECO:0000269|PubMed:23776469, ECO:0000269|PubMed:24225953}.
CC -!- DISRUPTION PHENOTYPE: Leads to a reduction of both roquefortine C and
CC meleagrin synthesis (PubMed:22118684, PubMed:23776469). Accumulates HTD
CC and roquefortine D (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 cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AM920436; CAP96444.1; -; Genomic_DNA.
DR RefSeq; XP_002568557.1; XM_002568511.1.
DR AlphaFoldDB; B6HJU5; -.
DR SMR; B6HJU5; -.
DR STRING; 1108849.XP_002568557.1; -.
DR EnsemblFungi; CAP96444; CAP96444; PCH_Pc21g15470.
DR GeneID; 8315548; -.
DR KEGG; pcs:Pc21g15470; -.
DR VEuPathDB; FungiDB:PCH_Pc21g15470; -.
DR eggNOG; KOG0159; Eukaryota.
DR HOGENOM; CLU_042557_2_0_1; -.
DR OMA; YWRFGFG; -.
DR OrthoDB; 825914at2759; -.
DR BioCyc; PCHR:PC21G15470-MON; -.
DR Proteomes; UP000000724; Contig Pc00c21.
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; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..511
FT /note="Cytochrome P450 monooxygenase roqR"
FT /id="PRO_5002845764"
FT BINDING 455
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 364
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 373
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 383
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 511 AA; 57767 MW; F2C2D2F86F487B78 CRC64;
MSGYVLLTVQ LAAVLLLVTL WRAFRPNTRS NRVVSYIINV GNTPKIHQKN KADFHPRTNV
EISPLVVPNL FDRWLNAHSD LPLSISRWRG KYQVPGGGER LPILTGADEI KAVFKDSGNH
RKASNLNGGW VMGDLVGDGV GLISEGHWKR VHAVVSPPFT QKPTTYVPFV QSRISRHFSE
LYPEDEGGRT LRIKPAEDLK LLPFWVISDL LYGNLSPEMT EELLQITDLR TDVFRYAFKG
GLSLFSISKI FYPDIRNKLH VFHTRWANFN RKAYQCALNR DDASACAIVT LYRAVEQGQI
TPTELMHTLD EALFANIDVT IGSFSWIPQF LAEDAALQSK LRKEISHARS DTAPESWVKY
IGSNSTLLAS CINESARLKP VTNYTYAQSM PTDRDVGGYR IPRGTFMVVD TNALNIWDDA
WGSDKTSYRP QRFLEESRAS FRYRFWRFGF GPRQCIAQAL ADTILKVLVA YTVENYELKS
TGKSAANEED AHKQGEAWFK VAEQGIILEA L
