Genomic mining for Aspergillus natural products

Chem Biol. 2006 Jan;13(1):31-7. doi: 10.1016/j.chembiol.2005.10.008.

Abstract

The genus Aspergillus is renowned for its ability to produce a myriad of bioactive secondary metabolites. Although the propensity of biosynthetic genes to form contiguous clusters greatly facilitates assignment of putative secondary metabolite genes in the completed Aspergillus genomes, such analysis cannot predict gene expression and, ultimately, product formation. To circumvent this deficiency, we have examined Aspergillus nidulans microarrays for expressed secondary metabolite gene clusters by using the transcriptional regulator LaeA. Deletion or overexpression of laeA clearly identified numerous secondary metabolite clusters. A gene deletion in one of the clusters eliminated the production of the antitumor compound terrequinone A, a metabolite not described, from A. nidulans. In this paper, we highlight that LaeA-based genome mining helps decipher the secondary metabolome of Aspergilli and provides an unparalleled view to assess secondary metabolism gene regulation.

Publication types

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

MeSH terms

  • Aspergillus nidulans / genetics*
  • Aspergillus nidulans / metabolism*
  • Biological Products / genetics*
  • Biological Products / isolation & purification
  • Gene Expression Regulation, Fungal / genetics
  • Genes, Fungal / genetics*
  • Genomics*
  • Indoles / chemistry
  • Indoles / metabolism
  • Molecular Structure
  • Multigene Family / genetics
  • Mutation / genetics
  • Oligonucleotide Array Sequence Analysis

Substances

  • Biological Products
  • Indoles
  • terrequinone A