F5HN73 · CPAD_ASPOZ

Function

function

Cyclo-acetoacetyl-L-tryptophan dimethylallyltransferase; 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).

Catalytic activity

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
109 μML-c-AATrp
3829 μMD-c-AATrp

Pathway

Secondary metabolite biosynthesis.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site84-85L-tryptophan (UniProtKB | ChEBI)
Binding site93L-tryptophan (UniProtKB | ChEBI)
Binding site104substrate
Binding site191substrate
Binding site193substrate
Binding site195L-tryptophan (UniProtKB | ChEBI)
Binding site258substrate
Binding site260substrate
Binding site262substrate
Binding site344substrate
Binding site346substrate
Binding site410substrate
Binding site414substrate

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Cyclo-acetoacetyl-L-tryptophan dimethylallyltransferase cpaD
  • EC number
  • Alternative names
    • Cyclopiazonic acid biosynthesis cluster protein D
    • L-tryptophan dimethylallyl transferase
      (DMATS
      )

Gene names

    • Name
      cpaD

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
    F5HN73

Organism-specific databases

Phenotypes & Variants

Disruption phenotype

Impairs the production of cyclopiazonic acid and of its biosynthetic intermediate beta-cyclopiazonic acid, but accumulates the intermediate cyclo-acetoacetyl-L-tryptophan.

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004453861-437Cyclo-acetoacetyl-L-tryptophan dimethylallyltransferase cpaD

Structure

Family & Domains

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    437
  • Mass (Da)
    49,186
  • Last updated
    2011-07-27 v1
  • Checksum
    67CAB188CDDDDDA0
MEISKKAATLLPKPFYVLSQALNLSNKDHTKWWYSTAPMFATMMAGAGYDVHAQYKFLCIHREVIIPALGPYPEKGQPMHWKSHLTRFGLPFELSFNYSKSLLRFAFEPLGSLTGTKDDPFNTQAIRPVLQDLKAMVPGLDLEWFDHFTKALVVSEEEARTLLDRDIEIPVFKTQNKLAADLEPSGDIVLKTYIYPRIKSIATGTPKERLMFDAIKAADKFGKVATPLAILEEFIAERAPTLLGHFLSCDLVKPSESRIKVYCMERQLDLASIEGIWTLNGRRNDPETLDGLDALRELWQLLPVTEGLCPLPNCFYEPGTSPQEQLPFIINFTLSPKSALPEPQIYFPAFGQNDKTIAEGLATFFESRGWGGLAKSYPADLASYYPDVDLQTANHLQAWISFSYKGKKPYMSVYLHTFEAFSAAAQEVAMCHDGHNP

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AB506492
EMBL· GenBank· DDBJ
BAK26561.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

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