Discovery of cryptic polyketide metabolites from dermatophytes using heterologous expression in Aspergillus nidulans

ACS Synth Biol. 2013 Nov 15;2(11):629-34. doi: 10.1021/sb400048b. Epub 2013 Jun 11.

Abstract

Dermatophytes belonging to the Trichophyton and Arthroderma genera cause skin infections in humans and animals. From genome sequencing data, we mined a conserved gene cluster among dermatophytes that are homologous to one that produces an immunosuppressive polyketide in Aspergillus fumigatus. Using a recombination-based cloning strategy in yeast, we constructed fungal heterologous expression vectors that encode the cryptic clusters. When integrated into the model Aspergillus nidulans host, a structurally related compound neosartoricin B was formed, suggesting a possible role of this compound in the pathogenesis of these strains.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Arthrodermataceae / chemistry*
  • Arthrodermataceae / genetics
  • Aspergillus nidulans / genetics*
  • Aspergillus nidulans / metabolism
  • Cloning, Molecular
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Genes, Fungal
  • Multigene Family*
  • Mutation
  • Polyketide Synthases / genetics
  • Polyketide Synthases / metabolism
  • Polyketides / metabolism
  • Secondary Metabolism

Substances

  • Fungal Proteins
  • Polyketides
  • Polyketide Synthases