ROQN_PENRW
ID ROQN_PENRW Reviewed; 288 AA.
AC B6HJU2;
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=Glandicoline B O-methyltransferase roqN {ECO:0000305};
DE EC=3.1.1.- {ECO:0000269|PubMed:22118684, ECO:0000269|PubMed:23776469, ECO:0000269|PubMed:24225953};
DE AltName: Full=Roquefortine/meleagrin synthesis protein N {ECO:0000303|PubMed:23776469};
GN Name=roqN {ECO:0000303|PubMed:23776469};
GN Synonyms=gmt {ECO:0000303|PubMed:22118684}; ORFNames=Pc21g15440;
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, 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: Glandicoline B O-methyltransferase; part of the gene cluster
CC that mediates the biosynthesis of the mycotoxin meleagrin
CC (PubMed:22118684, PubMed:23776469). The first stage is catalyzed by the
CC dipeptide synthase roqA which condenses histidine and tryptophan to
CC produce 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 -!- CATALYTIC ACTIVITY:
CC Reaction=glandicoline B + S-adenosyl-L-methionine = H(+) + meleagrin +
CC S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:51732, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:70399,
CC ChEBI:CHEBI:134347; Evidence={ECO:0000269|PubMed:22118684};
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 the accumulation of glandicoline B
CC (PubMed:22118684, PubMed:23776469). Does not affect the production of
CC roquefortine C but decreases the production of meleagrin
CC (PubMed:22118684, PubMed:24225953,PubMed:23776469).
CC {ECO:0000269|PubMed:22118684, ECO:0000269|PubMed:23776469,
CC 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 class I-like SAM-binding methyltransferase
CC superfamily. {ECO:0000305}.
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DR EMBL; AM920436; CAP96441.1; -; Genomic_DNA.
DR RefSeq; XP_002568554.1; XM_002568508.1.
DR PDB; 5W7M; X-ray; 1.70 A; A=1-288.
DR PDBsum; 5W7M; -.
DR AlphaFoldDB; B6HJU2; -.
DR SMR; B6HJU2; -.
DR STRING; 1108849.XP_002568554.1; -.
DR EnsemblFungi; CAP96441; CAP96441; PCH_Pc21g15440.
DR GeneID; 8315545; -.
DR KEGG; pcs:Pc21g15440; -.
DR VEuPathDB; FungiDB:PCH_Pc21g15440; -.
DR eggNOG; ENOG502S4V1; Eukaryota.
DR HOGENOM; CLU_065416_0_0_1; -.
DR OMA; HEMLPDW; -.
DR OrthoDB; 785883at2759; -.
DR BioCyc; PCHR:PC21G15440-MON; -.
DR Proteomes; UP000000724; Contig Pc00c21.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR041698; Methyltransf_25.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF13649; Methyltransf_25; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Methyltransferase; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..288
FT /note="Glandicoline B O-methyltransferase roqN"
FT /id="PRO_0000436348"
FT BINDING 57
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A6VDI6"
FT BINDING 82
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A6VDI6"
FT BINDING 109..110
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A6VDI6"
FT HELIX 17..27
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 28..30
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 31..38
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:5W7M"
FT STRAND 46..53
FT /evidence="ECO:0007829|PDB:5W7M"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 59..67
FT /evidence="ECO:0007829|PDB:5W7M"
FT TURN 68..70
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:5W7M"
FT STRAND 76..83
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 85..98
FT /evidence="ECO:0007829|PDB:5W7M"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:5W7M"
FT STRAND 120..127
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 135..145
FT /evidence="ECO:0007829|PDB:5W7M"
FT STRAND 146..159
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 162..171
FT /evidence="ECO:0007829|PDB:5W7M"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 182..186
FT /evidence="ECO:0007829|PDB:5W7M"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:5W7M"
FT TURN 191..194
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 196..206
FT /evidence="ECO:0007829|PDB:5W7M"
FT STRAND 209..223
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 224..231
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 235..242
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 245..251
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:5W7M"
FT HELIX 255..267
FT /evidence="ECO:0007829|PDB:5W7M"
FT STRAND 272..285
FT /evidence="ECO:0007829|PDB:5W7M"
SQ SEQUENCE 288 AA; 32277 MW; 825514F747E2E58C CRC64;
MTRATNFTEL YAGKGILDTY MVAEKITRYY TQDLIQLSGL SESSLTPLVI LDLACGTGVV
SDALHDMLNF QPKGNWELTC GDISTELTGH VKQKILERGW ENSIAKVVDA QNTELPTGHY
THVFAALAFT SFPDTYAAMK EVMRILQPGG TLTISTWQRT EWLAVVEAAV AIIPADLPFP
TTKEFMSCMN PGWDSEDYVH SRFEEAGFHS VQVTTISKQF ETSVEDLYKI AQPVIPIIVS
KWWNQEQRDK YENDILPALQ RHLNETYGEN GLVPQEWTAV FATGQKGS
