C9K203 · CPAM_ASPOZ

Function

function

Putative methyltransferase; part of the gene cluster that mediates the biosynthesis of the fungal neurotoxin cyclopiazonic acid (CPA), a nanomolar inhibitor of Ca2+-ATPase with a unique pentacyclic indole tetramic acid scaffold (PubMed:21608094).
The hybrid two module polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) cpaS incorporates acetyl-CoA, malonyl-CoA, and tryptophan (Trp) and utilizes a C-terminal redox-incompetent reductase domain to make and release the tryptophan tetramic acid, cyclo-acetoacetyl-L-tryptophan (c-AATrp), as the first intermediate in the pathway. CpaS catalyzes a Dieckmann-type cyclization on the N-acetoacetyl-Trp intermediate bound in thioester linkage to the phosphopantetheinyl arm of the T domain to form and release c-AATrp (PubMed:19663400, PubMed:21608094).
CpaD then regiospecifically dimethylallylates c-AATrp to form beta-cyclopiazonic acid. CpaD discriminates against free Trp but accepts tryptophan-containing thiohydantoins, diketopiperazines, and linear peptides as substrates for C4-prenylation and also acts as a regiospecific O-dimethylallyltransferase (DMAT) on a tyrosine-derived tetramic acid (PubMed:19877600, PubMed:21608094).
The beta-cyclopiazonate dehydrogenase cpaO then carries out the dehydrogenation of beta-CPA to yield an unstable enimine product, which is captured by intramolecular cyclization to create the pentacyclic fused scaffold of alpha-cyclopiazonate (PubMed:21608094).
Finally, the cytochrome P450 monooxygenase cpaH mediates the conversion of CPA into the less toxic 2-oxocyclopiazonic acid, the end product of the CPA pathway in A.oryza (PubMed:21608094).
The putative methyltransferase cpaM does not seem to be involved in CPA nor 2-oxocyclopiazonic acid biosynthesis (PubMed:21608094).

GO annotations

AspectTerm
Molecular Functionmethyltransferase activity
Biological Processmethylation

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Putative methyltransferase cpaM
  • EC number
  • Alternative names
    • Cyclopiazonic acid biosynthesis cluster protein M

Gene names

    • Name
      cpaM

Organism names

  • Taxonomic identifier
  • Strain
    • NBRC 4177
  • Taxonomic lineage
    Eukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus > Aspergillus subgen. Circumdati

Accessions

  • Primary accession
    C9K203

Organism-specific databases

Phenotypes & Variants

Disruption phenotype

Has no significant effect on the synthesis of 2-oxocyclopiazonic acid, cyclopiazonic acid (CPA) and their biosynthetic intermediates.

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004453881-434Putative methyltransferase cpaM

Family & Domains

Sequence similarities

Belongs to the methyltransferase superfamily.

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    434
  • Mass (Da)
    48,722
  • Last updated
    2009-11-24 v1
  • Checksum
    E3AEE6EE97AD8842
MKIGLLVLRGDPVEGPSVVDLSSYIPPSRHQFETRYISKSEAEAGIDRICKDEFDMCLNYMTVESCDDVSTVAAITRYLEAKDITLLNSPCLTHITDAGEETRRFRIPIKAHELNLEDLRGKKWLTLAMDMGREAMSFSPGQFTSSMCLDQEDLHSTSTDFTWVTEDPLKSMLRSMALDVLKASSGGFVCVEASLQAQADSMYLEGLLCTPRAFYREKHSTYEDVVIEQEFPGGHLAFLDMLITSKQIRSGQDHARNQHLAGVYDSFAPRYHAARANTGLSRMQEDMSRDYDFSGTVLDLACGNGEFGATLHENGVSAKVTGIDVSEGMTRSSYIQDHYERPLLIGPMDELIMGMPEFDHVSVTAIHEDLSDAYIEDMKKRNGELCSNFNHISTLEEFGVPNGWQQVLMQRFPLYENPNLGETVYGFAIRFERA

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AB454444
EMBL· GenBank· DDBJ
BAI43484.1
EMBL· GenBank· DDBJ
Genomic DNA
AB506492
EMBL· GenBank· DDBJ
BAK26558.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

Disclaimer

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