CNSA_PENEN
ID CNSA_PENEN Reviewed; 463 AA.
AC A0A0A2KMZ4;
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=Aurantioclavine synthase cnsA {ECO:0000303|PubMed:25571861};
DE EC=1.-.-.- {ECO:0000269|PubMed:25571861};
DE AltName: Full=Communesin biosynthesis cluster protein A {ECO:0000303|PubMed:25571861};
DE AltName: Full=FAD-linked oxidoreductase cnsA {ECO:0000303|PubMed:25571861};
GN Name=cnsA {ECO:0000303|PubMed:25571861}; ORFNames=PEX2_055350;
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: FAD-linked oxidoreductase; part of the gene cluster that
CC mediates the biosynthesis of communesins, a prominent class of indole
CC alkaloids with great potential as pharmaceuticals (PubMed:25571861).
CC Communesins are biosynthesized by the coupling of tryptamine and
CC aurantioclavine, two building blocks derived from L-tryptophan
CC (PubMed:25571861). The L-tryptophan decarboxylase cnsB converts L-
CC 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=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:25571861}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the biosynthesis of communesins A and B
CC and leads to the accumulation of 4-dimethylallyl tryptophan (4-DMAT).
CC {ECO:0000269|PubMed:25571861}.
CC -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; JQFZ01000090; KGO59694.1; -; Genomic_DNA.
DR RefSeq; XP_016600807.1; XM_016742809.1.
DR AlphaFoldDB; A0A0A2KMZ4; -.
DR SMR; A0A0A2KMZ4; -.
DR STRING; 27334.A0A0A2KMZ4; -.
DR EnsemblFungi; KGO40470; KGO40470; PEXP_030460.
DR EnsemblFungi; KGO59694; KGO59694; PEX2_055350.
DR EnsemblFungi; KGO69144; KGO69144; PEX1_005870.
DR GeneID; 27678228; -.
DR HOGENOM; CLU_590656_0_0_1; -.
DR OrthoDB; 827142at2759; -.
DR PhylomeDB; A0A0A2KMZ4; -.
DR Proteomes; UP000030143; Unassembled WGS sequence.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR012951; BBE.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR Pfam; PF08031; BBE; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Oxidoreductase; Reference proteome.
FT CHAIN 1..463
FT /note="Aurantioclavine synthase cnsA"
FT /id="PRO_0000446452"
FT DOMAIN 16..199
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
SQ SEQUENCE 463 AA; 51122 MW; E507E2D05345FAB3 CRC64;
MEGCTTRDST GLGLGERFNQ RGNVFLRLVS HVQCAIKFAK NHNLRLVIRN TGHDGSGRSS
APGSFEIHTH HLKHTHYHDD FQPVGAVTTS GPAVTVGAGV ILGDLYAEGA RQGYTVVGGV
CPTVGFVGGF LQGGGVSGKF SHNRGLAVDN VLEIQAVTAD GDLVVANDYH NQDLFWALRG
GGGGTFAVVT QATVRVFPDV PCVTTQLAVS APEGLDDHSW MQVLELLLRG LRSFNEERIA
GEFHLRPDPL SAILTLHFLN TSDLDSVDRR LAALIDKFRT SEIPHIYSSK SHALEVPRSV
EAKLYASHEL TSVQMPVLYS LDPSYKVSYL NMGDPNDADF RNVYWGPNYE RLLALKQKWD
VDALFITRLG KRHDVMNTIP STGAGADMRS FNRDIYDLLR NHAEDPRLNE VWTAINTVTE
WVDWITSNGA RMIPSDIAFR FWMLRVYMTH DWGCGLTSST AEL
