ROQM_PENRW
ID ROQM_PENRW Reviewed; 457 AA.
AC B6HJU4;
DT 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=FAD-dependent monooxygenase roqM {ECO:0000305};
DE EC=1.-.-.- {ECO:0000269|PubMed:22118684, ECO:0000269|PubMed:23776469, ECO:0000269|PubMed:24225953};
DE AltName: Full=Roquefortine/meleagrin synthesis protein M {ECO:0000303|PubMed:23776469};
GN Name=roqM {ECO:0000303|PubMed:23776469}; ORFNames=Pc21g15460;
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
RC {ECO:0000312|Proteomes:UP000000724};
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, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
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: FAD-dependent monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of the mycotoxin meleagrin (PubMed:22118684,
CC PubMed:23776469). The first stage is catalyzed by the dipeptide
CC synthase roqA which condenses histidine and tryptophan to produce
CC histidyltryptophanyldiketopiperazine (HTD) (PubMed:22118684,
CC PubMed:23776469). HTD is then converted to roquefortine C through two
CC possible pathways (PubMed:23776469). In the first pathway,
CC prenyltransferase roqD transforms HTD to the intermediate roquefortine
CC D, which is in turn converted to roquefortine C by the cytochrome P450
CC monooxygenase roqR (PubMed:23776469). In the second pathway, HTD is
CC first converted to the intermediate dehydrohistidyltryptophanyldi-
CC ketopiperazine (DHTD) by roqR which is then prenylated by roqD to form
CC roquefortine C (PubMed:23776469). Roquefortine C can be further
CC transformed to meleagrin via three more reactions including oxydation
CC to glandicolin A by roqM, which is further reduced to glandicoline B by
CC roqO (PubMed:23776469). Finally, glandicoline B is converted to
CC meleagrin by the glandicoline B O-methyltransferase roqN
CC (PubMed:22118684, PubMed:23776469). More studies identified further
CC 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=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
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 reduction of meleagrin synthesis
CC (PubMed:22118684). Accumulates roquefortine D and roquefortine C
CC (PubMed:23776469, PubMed:24225953). {ECO:0000269|PubMed:22118684,
CC ECO:0000269|PubMed:23776469, ECO:0000269|PubMed:24225953}.
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 paxM FAD-dependent monooxygenase family.
CC {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; AM920436; CAP96443.1; -; Genomic_DNA.
DR RefSeq; XP_002568556.1; XM_002568510.1.
DR AlphaFoldDB; B6HJU4; -.
DR SMR; B6HJU4; -.
DR STRING; 1108849.XP_002568556.1; -.
DR EnsemblFungi; CAP96443; CAP96443; PCH_Pc21g15460.
DR GeneID; 8315547; -.
DR KEGG; pcs:Pc21g15460; -.
DR VEuPathDB; FungiDB:PCH_Pc21g15460; -.
DR eggNOG; KOG2614; Eukaryota.
DR HOGENOM; CLU_009665_19_1_1; -.
DR OMA; KTRERWH; -.
DR OrthoDB; 462247at2759; -.
DR BioCyc; PCHR:PC21G15460-MON; -.
DR Proteomes; UP000000724; Contig Pc00c21.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Monooxygenase; Oxidoreductase; Reference proteome.
FT CHAIN 1..457
FT /note="FAD-dependent monooxygenase roqM"
FT /id="PRO_0000436346"
FT BINDING 321
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 331..335
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
SQ SEQUENCE 457 AA; 49893 MW; 5FC2DF79952F3359 CRC64;
MTVAHGVGPN GVAPPGSSGI QVIIVGLGIA GLVAAIECHY KGHVVVGLER SPGIRVLGSN
ATKVLQSWNN GEVLRHLVSQ SDDVAAMEIL DPAGKLYALD SMDGYGMGEG MIIHRGTLVH
GLYEHAKSLG IDLRFASAAT DYWEDEGQAG VTVNGEQRIA AACVVGADGV HSKTRDYVLG
YQIAPQPSGL AAFRACFSAN LLAGDPDAQW ILEEAGVQDR MRRYITTGGL GLTLSTGKRG
QNVIWQVWHR KHEKADESWE NVTDARVEDA LALLQDWPTY PQVAAVLRHT PSEKLADYKI
ISRDPLPTWR SRGGRIMVIG DAAHAMSAIA GQGGGQSVED AATLAICLEL AGKSRVNLAL
HVVERIRYQR TSIIQDSGNA IYSQMRDPDW ETIEKDPSMM KFPRPEWLFG YDVHRDVYEQ
FPYAMRAVQD NTGYRPRNIP SNSKYQVVHD YEKPVAA
