Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation

Hans-Wilhelm Nuetzmann, Yazmid Reyes-Dominguez, Kirstin Scherlach, Volker Schroeckh, Fabian Horn, Agnieszka Gacek, Julia Schümann, Christian Hertweck, Joseph Strauss, Axel A Brakhage

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

Sequence analyses of fungal genomes have revealed that the potential of fungi to produce secondary metabolites is greatly underestimated. In fact, most gene clusters coding for the biosynthesis of antibiotics, toxins, or pigments are silent under standard laboratory conditions. Hence, it is one of the major challenges in microbiology to uncover the mechanisms required for pathway activation. Recently, we discovered that intimate physical interaction of the important model fungus Aspergillus nidulans with the soil-dwelling bacterium Streptomyces rapamycinicus specifically activated silent fungal secondary metabolism genes, resulting in the production of the archetypal polyketide orsellinic acid and its derivatives. Here, we report that the streptomycete triggers modification of fungal histones. Deletion analysis of 36 of 40 acetyltransferases, including histone acetyltransferases (HATs) of A. nidulans, demonstrated that the Saga/Ada complex containing the HAT GcnE and the AdaB protein is required for induction of the orsellinic acid gene cluster by the bacterium. We also showed that Saga/Ada plays a major role for specific induction of other biosynthesis gene clusters, such as sterigmatocystin, terrequinone, and penicillin. Chromatin immunoprecipitation showed that the Saga/Ada-dependent increase of histone 3 acetylation at lysine 9 and 14 occurs during interaction of fungus and bacterium. Furthermore, the production of secondary metabolites in A. nidulans is accompanied by a global increase in H3K14 acetylation. Increased H3K9 acetylation, however, was only found within gene clusters. This report provides previously undescribed evidence of Saga/Ada dependent histone acetylation triggered by prokaryotes.

Original languageEnglish
Pages (from-to)14282-7
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number34
DOIs
Publication statusPublished - 23 Aug 2011

Keywords

  • Acetylation
  • Aspergillus nidulans
  • Biocatalysis
  • Biological Products
  • Fungal Proteins
  • Gene Deletion
  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Histone Acetyltransferases
  • Histones
  • Models, Biological
  • Multigene Family
  • Promoter Regions, Genetic
  • Resorcinols
  • Salicylates
  • Sterigmatocystin
  • Streptomyces
  • Journal Article
  • Research Support, Non-U.S. Gov't

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