CNSE_PENEN
ID CNSE_PENEN Reviewed; 276 AA.
AC A0A0A2IBN3;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 04-FEB-2015, sequence version 1.
DT 03-AUG-2022, entry version 27.
DE RecName: Full=O-methyltransferase cnsE {ECO:0000303|PubMed:25571861};
DE EC=2.1.1.- {ECO:0000269|PubMed:25571861};
DE AltName: Full=Communesin biosynthesis cluster protein E {ECO:0000303|PubMed:25571861};
GN Name=cnsE {ECO:0000303|PubMed:25571861}; ORFNames=PEX2_055390;
OS Penicillium expansum (Blue mold rot fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=27334;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MD-8;
RX PubMed=25338147; DOI=10.1094/MPMI-09-14-0261-FI;
RA Ballester A.R., Marcet-Houben M., Levin E., Sela N., Selma-Lazaro C.,
RA Carmona L., Wisniewski M., Droby S., Gonzalez-Candelas L., Gabaldon T.;
RT "Genome, transcriptome, and functional analyses of Penicillium expansum
RT provide new insights into secondary metabolism and pathogenicity.";
RL Mol. Plant Microbe Interact. 28:232-248(2015).
RN [2]
RP IDENTIFICATION, FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RX PubMed=25571861; DOI=10.1002/anie.201411297;
RA Lin H.C., Chiou G., Chooi Y.H., McMahon T.C., Xu W., Garg N.K., Tang Y.;
RT "Elucidation of the concise biosynthetic pathway of the communesin indole
RT alkaloids.";
RL Angew. Chem. Int. Ed. 54:3004-3007(2015).
RN [3]
RP FUNCTION.
RX PubMed=26963294; DOI=10.1021/jacs.6b01413;
RA Lin H.C., McMahon T.C., Patel A., Corsello M., Simon A., Xu W., Zhao M.,
RA Houk K.N., Garg N.K., Tang Y.;
RT "P450-mediated coupling of indole fragments to forge communesin and
RT unnatural isomers.";
RL J. Am. Chem. Soc. 138:4002-4005(2016).
CC -!- FUNCTION: O-methyltransferase; part of the gene cluster that mediates
CC the biosynthesis of communesins, a prominent class of indole alkaloids
CC with great potential as pharmaceuticals (PubMed:25571861). Communesins
CC are biosynthesized by the coupling of tryptamine and aurantioclavine,
CC two building blocks derived from L-tryptophan (PubMed:25571861). The L-
CC tryptophan decarboxylase cnsB converts L-tryptophan to tryptamine,
CC whereas the tryptophan dimethylallyltransferase cnsF converts L-
CC tryptophan to 4-dimethylallyl tryptophan which is further transformed
CC to aurantioclavine by the aurantioclavine synthase cnsA, probably aided
CC by the catalase cnsD (PubMed:25571861). The cytochrome P450
CC monooxygenase cnsC catalyzes the heterodimeric coupling between the two
CC different indole moieties, tryptamine and aurantioclavine, to construct
CC vicinal quaternary stereocenters and yield the heptacyclic communesin
CC scaffold (PubMed:26963294). The O-methyltransferase cnsE then
CC methylates the communesin scaffold to produce communesin K, the
CC simplest characterized communesin that contains the heptacyclic core
CC (PubMed:25571861). The dioxygenase cnsJ converts communesin K into
CC communesin I (PubMed:25571861). Acylation to introduce the hexadienyl
CC group at position N16 of communesin I by the acyltransferase cnsK leads
CC to the production of communesin B. The hexadienyl group is produced by
CC the highly reducing polyketide synthase cnsI, before being
CC hydrolytically removed from cnsI by the serine hydrolase cnsH,
CC converted into hexadienyl-CoA by the CoA ligase cnsG, and then
CC transferred to communesin I by cnsK (PubMed:25571861). Surprisingly,
CC cnsK may also be a promiscuous acyltransferase that can tolerate a
CC range of acyl groups, including acetyl-, propionyl-, and butyryl-CoA,
CC which lead to communesins A, G and H respectively (PubMed:25571861).
CC The roles of the alpha-ketoglutarate-dependent dioxygenases cnsM and
CC cnsP have still to be determined (PubMed:25571861).
CC {ECO:0000269|PubMed:25571861, ECO:0000269|PubMed:26963294}.
CC -!- COFACTOR:
CC Name=S-adenosyl-L-methionine; Xref=ChEBI:CHEBI:59789;
CC Evidence={ECO:0000250|UniProtKB:Q8KZ94};
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000305|PubMed:25571861}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the biosynthesis of communesins A and B
CC and leads to the accumulation of desmethyl versions of communesins A
CC and B, including communesin C. {ECO:0000269|PubMed:25571861}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC {ECO:0000305}.
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DR EMBL; JQFZ01000090; KGO59698.1; -; Genomic_DNA.
DR RefSeq; XP_016600811.1; XM_016742813.1.
DR AlphaFoldDB; A0A0A2IBN3; -.
DR SMR; A0A0A2IBN3; -.
DR EnsemblFungi; KGO40474; KGO40474; PEXP_030500.
DR EnsemblFungi; KGO50066; KGO50066; PEX1_082050.
DR EnsemblFungi; KGO59698; KGO59698; PEX2_055390.
DR GeneID; 27678232; -.
DR HOGENOM; CLU_039068_6_0_1; -.
DR OrthoDB; 785883at2759; -.
DR PhylomeDB; A0A0A2IBN3; -.
DR Proteomes; UP000030143; Unassembled WGS sequence.
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; IPR013216; Methyltransf_11.
DR InterPro; IPR020803; PKS_MeTfrase.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF08241; Methyltransf_11; 1.
DR SMART; SM00828; PKS_MT; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..276
FT /note="O-methyltransferase cnsE"
FT /id="PRO_0000446460"
FT BINDING 110
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8KZ94"
FT BINDING 133..134
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8KZ94"
FT BINDING 155
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8KZ94"
SQ SEQUENCE 276 AA; 29984 MW; 634AF625FA3DAA0E CRC64;
MASETENLRA IALDPSHPTP TDVGEIYDET SDSLTDMLGG YIHVGYWEDP SKQETAEVVG
DRLTREVGVR LSPAQGEHIL DVGCGTGKST AQLAGIYDAQ VTGITISKQQ VEVARSQYGR
KMPAGQVHFQ FADAMDLPFG DASFDGAYAI ESLVHMLDKR TALAQIAQVL RPGSRLVIAD
LVSDHPCPDS PVLARYAEIF EPPLVSADDL QNLLRQAGFK VIDVTDIREN IRPSCKLFET
KGLSLGGELG QKLLEIASIL EEMNELGYAL ITAERL
