ID   CNSG_PENEN              Reviewed;         481 AA.
AC   A0A0A2J5U8;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   04-FEB-2015, sequence version 1.
DT   03-AUG-2022, entry version 31.
DE   RecName: Full=Acyl-CoA ligase cnsG {ECO:0000303|PubMed:25571861};
DE            EC=6.2.1.- {ECO:0000305|PubMed:25571861};
DE   AltName: Full=Communesin biosynthesis cluster protein G {ECO:0000303|PubMed:25571861};
GN   Name=cnsG {ECO:0000303|PubMed:25571861}; ORFNames=PEX2_055410;
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: Acyl-CoA ligase; part of the gene cluster that mediates the
CC       biosynthesis of communesins, a prominent class of indole alkaloids with
CC       great potential as pharmaceuticals (PubMed:25571861). Communesins are
CC       biosynthesized by the coupling of tryptamine and aurantioclavine, two
CC       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   -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000305|PubMed:25571861}.
CC   -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC       {ECO:0000305}.
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DR   EMBL; JQFZ01000090; KGO59700.1; -; Genomic_DNA.
DR   RefSeq; XP_016600813.1; XM_016742815.1.
DR   AlphaFoldDB; A0A0A2J5U8; -.
DR   SMR; A0A0A2J5U8; -.
DR   STRING; 27334.A0A0A2J5U8; -.
DR   EnsemblFungi; KGO40476; KGO40476; PEXP_030520.
DR   EnsemblFungi; KGO50068; KGO50068; PEX1_082070.
DR   EnsemblFungi; KGO59700; KGO59700; PEX2_055410.
DR   GeneID; 27678234; -.
DR   HOGENOM; CLU_000022_59_7_1; -.
DR   OrthoDB; 386992at2759; -.
DR   PhylomeDB; A0A0A2J5U8; -.
DR   Proteomes; UP000030143; Unassembled WGS sequence.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.30.300.30; -; 1.
DR   Gene3D; 3.40.50.12780; -; 2.
DR   InterPro; IPR025110; AMP-bd_C.
DR   InterPro; IPR045851; AMP-bd_C_sf.
DR   InterPro; IPR000873; AMP-dep_Synth/Lig.
DR   InterPro; IPR042099; ANL_N_sf.
DR   Pfam; PF00501; AMP-binding; 2.
DR   Pfam; PF13193; AMP-binding_C; 1.
PE   3: Inferred from homology;
KW   ATP-binding; Ligase; Nucleotide-binding; Reference proteome.
FT   CHAIN           1..481
FT                   /note="Acyl-CoA ligase cnsG"
FT                   /id="PRO_0000446462"
FT   MOTIF           3..11
FT                   /note="PTS2-type peroxisomal targeting signal"
FT                   /evidence="ECO:0000250|UniProtKB:Q4WR83"
FT   BINDING         124..132
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT   BINDING         263..268
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT   BINDING         268
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT   BINDING         353
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT   BINDING         368
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT   BINDING         376..378
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT   BINDING         446..448
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT   BINDING         466
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q08AH3"
SQ   SEQUENCE   481 AA;  52897 MW;  79DA234ED10C301D CRC64;
     MESPQLPPSM KRPAIVYGDK TPTILETTLG HLLDELSDIH RDKAAVEFPW QSIRRTYSEL
     AKTSKLVAIS LLSAGLCHGD RIGILTGNRY EFLDVFLAAA RIGCPAVILQ SNMSPGEMKA
     AVLKSGTTGN PKAAVLTHRN VVNNSHFFSR ACDFEQSDII CSPLPLCHSF GLVSAFLCSF
     MRGCLILFPT EKFSADAVVD VLQNRDVTVI YGVPTMFFAV LEKLQGRGHK PRSMVKAIAG
     GAPVPYALIT QICQDMGVQY FLNGYGMTET SPATFISPLG LCSESSLRTI GKVLPHTNAR
     IVDRWGRTVQ QGEKGELCIS GLPLQKGYWE DEEKTSEIMT RDADGVIWLH TGDEAIIGED
     DHCTITGRIK DIIIRGGLNI SPVEIEERLI LHPFIQEASV VGLPDKTRGE IVGCFLKQYV
     DMQRPSDEAV RAWVRELLGW HKAPEAIFWI GDAGIGEDFP KTASGKHQKE KLKDIGTYLL
     A