CNSP_PENEN
ID CNSP_PENEN Reviewed; 370 AA.
AC A0A0A2IJP3;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 04-FEB-2015, sequence version 1.
DT 03-AUG-2022, entry version 29.
DE RecName: Full=Alpha-ketoglutarate-dependent dioxygenase cnsP {ECO:0000303|PubMed:25571861};
DE EC=1.14.11.-;
DE AltName: Full=Communesin biosynthesis cluster protein P {ECO:0000303|PubMed:25571861};
GN Name=cnsP {ECO:0000303|PubMed:25571861}; ORFNames=PEX2_055500;
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, AND 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: Alpha-ketoglutarate-dependent dioxygenase; part of the gene
CC cluster that mediates the biosynthesis of communesins, a prominent
CC class of 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 -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:P37610};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:P37610};
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000305|PubMed:25571861}.
CC -!- SIMILARITY: Belongs to the TfdA dioxygenase family. {ECO:0000305}.
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DR EMBL; JQFZ01000090; KGO59709.1; -; Genomic_DNA.
DR RefSeq; XP_016600822.1; XM_016742824.1.
DR AlphaFoldDB; A0A0A2IJP3; -.
DR SMR; A0A0A2IJP3; -.
DR EnsemblFungi; KGO40485; KGO40485; PEXP_030610.
DR EnsemblFungi; KGO59709; KGO59709; PEX2_055500.
DR EnsemblFungi; KGO63753; KGO63753; PEX1_037460.
DR GeneID; 27678243; -.
DR HOGENOM; CLU_036005_0_0_1; -.
DR OrthoDB; 694257at2759; -.
DR PhylomeDB; A0A0A2IJP3; -.
DR Proteomes; UP000030143; Unassembled WGS sequence.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR Gene3D; 3.60.130.10; -; 1.
DR InterPro; IPR042098; TauD-like_sf.
DR InterPro; IPR003819; TauD/TfdA-like.
DR Pfam; PF02668; TauD; 1.
PE 3: Inferred from homology;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..370
FT /note="Alpha-ketoglutarate-dependent dioxygenase cnsP"
FT /id="PRO_0000446469"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 131
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P37610"
FT BINDING 169
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P37610"
FT BINDING 171
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P37610"
FT BINDING 197
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:P37610"
FT BINDING 321
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P37610"
FT BINDING 333
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:P37610"
FT BINDING 337
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:P37610"
FT BINDING 337
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P37610"
SQ SEQUENCE 370 AA; 41455 MW; 8EB072581CF59EB7 CRC64;
MSTTTVITPG TITREKNENG APLYPDYMPF YDPLEKVEDI GAFEHFDPGH RADPKLPNLL
KNATKVWELS PHVGTEIHGV QLSQLDSAGL DELALLAAQR GALVFRDQDF VNIGFDAQKK
LVSHFGPLHI HGWAPHPAAG SEEHMIIYDH KDDLRVRQSW AGRSPVQWHT DQSPEQQPPG
TTFIAMLESP TTAGGDTLVS SSVRAYSSLS PRFRKRLEGL TAIHTNNDGV SQELKHGQQA
VMRRGVLQAE HPVVLVHPVT KQKALYVNPV YTKKIVGFDQ EESDCILKFL FDHIAKRQDF
SCRIRYEAGT VLVWDQRVTN HSQTLDYPIG DRRHGFRLTP LANKPIPAKI EEDDEEFSTD
DARHLVGNAS
