Chromatin-level regulation of biosynthetic gene clusters

Nat Chem Biol. 2009 Jul;5(7):462-4. doi: 10.1038/nchembio.177.

Abstract

Loss-of-function Aspergillus nidulans CclA, a Bre2 ortholog involved in histone H3 lysine 4 methylation, activated the expression of cryptic secondary metabolite clusters in A. nidulans. One new cluster generated monodictyphenone, emodin and emodin derivatives, whereas a second encoded two anti-osteoporosis polyketides, F9775A and F9775B. Modification of the chromatin landscape in fungal secondary metabolite clusters allows for a simple technological means to express silent fungal secondary metabolite gene clusters.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / biosynthesis
  • Anti-Bacterial Agents / chemistry
  • Aspergillus nidulans / enzymology
  • Aspergillus nidulans / genetics*
  • Aspergillus nidulans / metabolism
  • Chromatin / metabolism*
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Drug Discovery*
  • Emodin / chemistry
  • Gene Deletion
  • Gene Expression Regulation, Fungal*
  • Histones / metabolism
  • Immunoprecipitation
  • Macrolides / chemistry
  • Mass Spectrometry
  • Methylation
  • Molecular Structure
  • Multigene Family*
  • Polyketide Synthases / genetics
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic

Substances

  • Anti-Bacterial Agents
  • Chromatin
  • Histones
  • Macrolides
  • Polyketide Synthases
  • Emodin