C9K203 · CPAM_ASPOZ
- ProteinPutative methyltransferase cpaM
- GenecpaM
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids434 (go to sequence)
- Protein existenceInferred from homology
- Annotation score2/5
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).
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
Aspect | Term | |
---|---|---|
Molecular Function | methyltransferase activity | |
Biological Process | methylation |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePutative methyltransferase cpaM
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus > Aspergillus subgen. Circumdati
Accessions
- Primary accessionC9K203
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000445388 | 1-434 | Putative methyltransferase cpaM | |||
Sequence: MKIGLLVLRGDPVEGPSVVDLSSYIPPSRHQFETRYISKSEAEAGIDRICKDEFDMCLNYMTVESCDDVSTVAAITRYLEAKDITLLNSPCLTHITDAGEETRRFRIPIKAHELNLEDLRGKKWLTLAMDMGREAMSFSPGQFTSSMCLDQEDLHSTSTDFTWVTEDPLKSMLRSMALDVLKASSGGFVCVEASLQAQADSMYLEGLLCTPRAFYREKHSTYEDVVIEQEFPGGHLAFLDMLITSKQIRSGQDHARNQHLAGVYDSFAPRYHAARANTGLSRMQEDMSRDYDFSGTVLDLACGNGEFGATLHENGVSAKVTGIDVSEGMTRSSYIQDHYERPLLIGPMDELIMGMPEFDHVSVTAIHEDLSDAYIEDMKKRNGELCSNFNHISTLEEFGVPNGWQQVLMQRFPLYENPNLGETVYGFAIRFERA |
Structure
Sequence
- Sequence statusComplete
- Length434
- Mass (Da)48,722
- Last updated2009-11-24 v1
- ChecksumE3AEE6EE97AD8842