Genome-wide chromatin mapping of Aspergillus nidulans reveals BasR, a novel regulator of bacteria-triggered fungal natural product biosynthesis

Microorganisms can produce a plethora of secondary metabolites (SMs), which often have pharmacological potential (1). In nature, microorganisms live in multispecies communities, in which the produced SMs are often used as signal molecules. Mimicking the natural habitat in the laboratory by mixed fermentation experiments has been developed into a useful strategy to identify new SMs (2). We have been intensively studying the interaction between the model organism Aspergillus nidulans and the soil bacterium Streptomyces rapamycinicus, which leads to the activation of the silent fungal orsellinic acid (ors) gene cluster (3). Essential for the ors gene cluster activation is the activity of the lysine-acetyltransferase GcnE, which specifically acetylates lysine 9 and 14 of histone H3 during the co-cultivation (4). Furthermore we could show that the exchange of several amino acids of histone H3 in A. nidulans resulted in major changes in the penicillin, sterigmatocystin and orsellinic acid biosynthesis (5). This specific microbial interaction provides an excellent model system to study molecular and regulatory mechanisms underlying interspecies crosstalk. A genome-wide chromatin immunoprecipitation (ChIP) analysis was performed to analyse the distribution of the acetylation events during the interaction. Our data reveal major changes in the fungal chromatin landscape induced by the bacterium and led to the identification of the transcription factor BasR, required for the bacteria-induced activation of secondary metabolism.

(1) Macheleidt et al. (2016) Annu Rev Genet, (2) Netzker et al. (2015) Front Microbiol, (3) Schroeckh et al. (2009) PNAS, (4) Nützmann et al. (2011) PNAS, (5) Nützmann, Fischer et al. (2013) AEM