CPAM_ASPOZ
ID CPAM_ASPOZ Reviewed; 434 AA.
AC C9K203;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=Putative methyltransferase cpaM {ECO:0000303|PubMed:21608094};
DE EC=2.1.1.- {ECO:0000305|PubMed:21608094};
DE AltName: Full=Cyclopiazonic acid biosynthesis cluster protein M {ECO:0000303|PubMed:21608094};
GN Name=cpaM {ECO:0000303|PubMed:21608094};
OS Aspergillus oryzae (Yellow koji mold).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=5062;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RA Seshime Y., Juvvadi P.R., Tokuoka M., Koyama Y., Kitamoto K., Ebizuka Y.,
RA Fujii I.;
RT "Functional expression of the Aspergillus flavus PKS-NRPS hybrid CpaA
RT involved in the biosynthesis of cyclopiazonic acid.";
RL Submitted (AUG-2008) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], DISRUPTION PHENOTYPE, FUNCTION, AND
RP PATHWAY.
RC STRAIN=NBRC 4177;
RX PubMed=21608094; DOI=10.1002/cbic.201000672;
RA Kato N., Tokuoka M., Shinohara Y., Kawatani M., Uramoto M., Seshime Y.,
RA Fujii I., Kitamoto K., Takahashi T., Takahashi S., Koyama Y., Osada H.;
RT "Genetic safeguard against mycotoxin cyclopiazonic acid production in
RT Aspergillus oryzae.";
RL ChemBioChem 12:1376-1382(2011).
RN [3]
RP FUNCTION.
RX PubMed=19663400; DOI=10.1021/bi901123r;
RA Liu X., Walsh C.T.;
RT "Cyclopiazonic acid biosynthesis in Aspergillus sp.: characterization of a
RT reductase-like R* domain in cyclopiazonate synthetase that forms and
RT releases cyclo-acetoacetyl-L-tryptophan.";
RL Biochemistry 48:8746-8757(2009).
RN [4]
RP FUNCTION.
RX PubMed=19877600; DOI=10.1021/bi901597j;
RA Liu X., Walsh C.T.;
RT "Characterization of cyclo-acetoacetyl-L-tryptophan
RT dimethylallyltransferase in cyclopiazonic acid biosynthesis: substrate
RT promiscuity and site directed mutagenesis studies.";
RL Biochemistry 48:11032-11044(2009).
CC -!- FUNCTION: Putative methyltransferase; part of the gene cluster that
CC mediates the biosynthesis of the fungal neurotoxin cyclopiazonic acid
CC (CPA), a nanomolar inhibitor of Ca(2+)-ATPase with a unique pentacyclic
CC indole tetramic acid scaffold (PubMed:21608094). The hybrid two module
CC polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) cpaS
CC incorporates acetyl-CoA, malonyl-CoA, and tryptophan (Trp) and utilizes
CC a C-terminal redox-incompetent reductase domain to make and release the
CC tryptophan tetramic acid, cyclo-acetoacetyl-L-tryptophan (c-AATrp), as
CC the first intermediate in the pathway. CpaS catalyzes a Dieckmann-type
CC cyclization on the N-acetoacetyl-Trp intermediate bound in thioester
CC linkage to the phosphopantetheinyl arm of the T domain to form and
CC release c-AATrp (PubMed:21608094, PubMed:19663400). CpaD than
CC regiospecifically dimethylallylates c-AATrp to form beta-cyclopiazonic
CC acid. CpaD discriminates against free Trp but accepts tryptophan-
CC containing thiohydantoins, diketopiperazines, and linear peptides as
CC substrates for C4-prenylation and also acts as regiospecific O-
CC dimethylallyltransferase (DMAT) on a tyrosine-derived tetramic acid
CC (PubMed:21608094, PubMed:19877600). The beta-cyclopiazonate
CC dehydrogenase cpaO then carries out the dehydrogenation of beta-CPA to
CC yield an unstable enimine product, which is captured by intramolecular
CC cyclization to create the pentacyclic fused scaffold of alpha-
CC cyclopiazonate (PubMed:21608094). Fimally, the cytochrome P450
CC monooxygenase cpaH mediates the conversion of CPA into the less toxic
CC 2-oxocyclopiazonic acid, the end product of the CPA pathway in A.oryza
CC (PubMed:21608094). The putative methyltransferase cpaM does not seem to
CC be involved in CPA nor 2-oxocyclopiazonic acid biosynthesis
CC (PubMed:21608094). {ECO:0000269|PubMed:19663400,
CC ECO:0000269|PubMed:19877600, ECO:0000269|PubMed:21608094}.
CC -!- DISRUPTION PHENOTYPE: Has no significant effect on the synthesis of 2-
CC oxocyclopiazonic acid, cyclopiazonic acid (CPA) and their biosynthetic
CC intermediates. {ECO:0000269|PubMed:21608094}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB454444; BAI43484.1; -; Genomic_DNA.
DR EMBL; AB506492; BAK26558.1; -; Genomic_DNA.
DR AlphaFoldDB; C9K203; -.
DR VEuPathDB; FungiDB:AO090701001141; -.
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; IPR041698; Methyltransf_25.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF13649; Methyltransf_25; 1.
DR SUPFAM; SSF53335; SSF53335; 2.
PE 3: Inferred from homology;
KW Methyltransferase; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..434
FT /note="Putative methyltransferase cpaM"
FT /id="PRO_0000445388"
SQ SEQUENCE 434 AA; 48722 MW; E3AEE6EE97AD8842 CRC64;
MKIGLLVLRG DPVEGPSVVD LSSYIPPSRH QFETRYISKS EAEAGIDRIC KDEFDMCLNY
MTVESCDDVS TVAAITRYLE AKDITLLNSP CLTHITDAGE ETRRFRIPIK AHELNLEDLR
GKKWLTLAMD MGREAMSFSP GQFTSSMCLD QEDLHSTSTD FTWVTEDPLK SMLRSMALDV
LKASSGGFVC VEASLQAQAD SMYLEGLLCT PRAFYREKHS TYEDVVIEQE FPGGHLAFLD
MLITSKQIRS GQDHARNQHL AGVYDSFAPR YHAARANTGL SRMQEDMSRD YDFSGTVLDL
ACGNGEFGAT LHENGVSAKV TGIDVSEGMT RSSYIQDHYE RPLLIGPMDE LIMGMPEFDH
VSVTAIHEDL SDAYIEDMKK RNGELCSNFN HISTLEEFGV PNGWQQVLMQ RFPLYENPNL
GETVYGFAIR FERA
