CNSF_PENEN
ID CNSF_PENEN Reviewed; 453 AA.
AC A0A0A2JWD0;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 04-FEB-2015, sequence version 1.
DT 03-AUG-2022, entry version 34.
DE RecName: Full=Tryptophan dimethylallyltransferase cnsF {ECO:0000303|PubMed:25571861};
DE EC=2.5.1.34 {ECO:0000269|PubMed:25571861};
DE AltName: Full=4-dimethylallyltryptophan synthase {ECO:0000303|PubMed:25571861};
DE Short=DMATS {ECO:0000303|PubMed:25571861};
DE AltName: Full=All-trans-hexaprenyl-diphosphate synthase {ECO:0000305};
DE AltName: Full=Communesin biosynthesis cluster protein F {ECO:0000303|PubMed:25571861};
DE AltName: Full=L-tryptophan dimethylallyl transferase {ECO:0000305};
GN Name=cnsF {ECO:0000303|PubMed:25571861}; ORFNames=PEX2_055400;
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: Tryptophan dimethylallyltransferase; part of the gene cluster
CC that mediates the biosynthesis of communesins, a prominent class of
CC indole alkaloids with great potential as pharmaceuticals
CC (PubMed:25571861). Communesins are biosynthesized by the coupling of
CC tryptamine and aurantioclavine, two building blocks derived from L-
CC tryptophan (PubMed:25571861). The L-tryptophan decarboxylase cnsB
CC converts L-tryptophan to tryptamine, whereas the tryptophan
CC dimethylallyltransferase cnsF converts L-tryptophan to 4-dimethylallyl
CC tryptophan which is further transformed to aurantioclavine by the
CC aurantioclavine synthase cnsA, probably aided by the catalase cnsD
CC (PubMed:25571861). The cytochrome P450 monooxygenase cnsC catalyzes the
CC heterodimeric coupling between the two different indole moieties,
CC tryptamine and aurantioclavine, to construct vicinal quaternary
CC stereocenters and yield the heptacyclic communesin scaffold
CC (PubMed:26963294). The O-methyltransferase cnsE then methylates the
CC communesin scaffold to produce communesin K, the simplest characterized
CC communesin that contains the heptacyclic core (PubMed:25571861). The
CC dioxygenase cnsJ converts communesin K into communesin I
CC (PubMed:25571861). Acylation to introduce the hexadienyl group at
CC position N16 of communesin I by the acyltransferase cnsK leads to the
CC production of communesin B. The hexadienyl group is produced by the
CC highly reducing polyketide synthase cnsI, before being hydrolytically
CC removed from cnsI by the serine hydrolase cnsH, converted into
CC hexadienyl-CoA by the CoA ligase cnsG, and then transferred to
CC communesin I by cnsK (PubMed:25571861). Surprisingly, cnsK may also be
CC a promiscuous acyltransferase that can tolerate a range of acyl groups,
CC including acetyl-, propionyl-, and butyryl-CoA, which lead to
CC communesins A, G and H respectively (PubMed:25571861). The roles of the
CC alpha-ketoglutarate-dependent dioxygenases cnsM and cnsP have still to
CC be determined (PubMed:25571861). {ECO:0000269|PubMed:25571861,
CC ECO:0000269|PubMed:26963294}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dimethylallyl diphosphate + L-tryptophan = 4-(3-methylbut-2-
CC enyl)-L-tryptophan + diphosphate; Xref=Rhea:RHEA:14173,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57623, ChEBI:CHEBI:57912,
CC ChEBI:CHEBI:58209; EC=2.5.1.34;
CC Evidence={ECO:0000269|PubMed:25571861};
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:25571861}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q50EL0}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the biosynthesis of communesins A and
CC B. {ECO:0000269|PubMed:25571861}.
CC -!- SIMILARITY: Belongs to the tryptophan dimethylallyltransferase family.
CC {ECO:0000305}.
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DR EMBL; JQFZ01000090; KGO59699.1; -; Genomic_DNA.
DR RefSeq; XP_016600812.1; XM_016742814.1.
DR AlphaFoldDB; A0A0A2JWD0; -.
DR SMR; A0A0A2JWD0; -.
DR STRING; 27334.A0A0A2JWD0; -.
DR EnsemblFungi; KGO40475; KGO40475; PEXP_030510.
DR EnsemblFungi; KGO50067; KGO50067; PEX1_082060.
DR EnsemblFungi; KGO59699; KGO59699; PEX2_055400.
DR GeneID; 27678233; -.
DR HOGENOM; CLU_037431_0_0_1; -.
DR OrthoDB; 1531660at2759; -.
DR PhylomeDB; A0A0A2JWD0; -.
DR Proteomes; UP000030143; Unassembled WGS sequence.
DR GO; GO:0004659; F:prenyltransferase activity; IEA:UniProt.
DR GO; GO:0050364; F:tryptophan dimethylallyltransferase activity; IEA:UniProtKB-EC.
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 Reference proteome; Transferase.
FT CHAIN 1..453
FT /note="Tryptophan dimethylallyltransferase cnsF"
FT /id="PRO_0000446461"
FT BINDING 84..85
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 93
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 104
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 190
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 192
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 194
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 248
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 261
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 263
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 265
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 347
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 349
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
SQ SEQUENCE 453 AA; 51691 MW; 1FB1FB9AD8A34D36 CRC64;
MGTHDMSPNA SHSYIYRVLS DILEFPDNEQ RMWWHSVAPM FAEMLRACGY DIHEQYKILG
IWKKAVIPFL GCYPTNDGPR WLSILTRYGT PFELSLNCSH RLVRYTFEPI NAATGTDKDP
FNTQAIWESL SQLRRLNGDV DTELFNHFKA NLTVDNAESA HLVESNLAGS KIRTQNKLAL
DLQNGSFVVK AYFYPTLKSA ATGRSITDLM LSSVRQQVQK WSPTLAQPLS VLEEYIEARG
PDSTASPRLL SCDLINPERA RTKIYLLERQ VSIEAMEDLW TLGGRRKSDS ALAALDIIRE
IWSLIQLPPC LASYPSGYLP LGTVPDEQLP LMVNYTLRPD DPMPEPQVYF TTFGQNDLHV
TNALTAFFER QGWTELAESY KENLRAYYPH ADQETANYIH AYVSFSYRKG VSYMSVYLQT
LETGDWPITY SPKRQYLCNE HPIHLKELAK ACA
