Molecular characterisation of BasR, a novel regulator of natural product biosynthesis in Aspergillus nidulans

Nils Jäger 1 Juliane Fischer 2 Kirstin Scherlach 3 Volker Schroeckh 2 Christian Hertweck 3,4 Thorsten Heinzel 1 Axel A. Brakhage 2,5
1Department of Biochemistry, Friedrich-Schiller-University Jena, Jena, Germany
2Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany
3Biomolecular Chemistry, Friedrich-Schiller-University Jena, Jena, Germany
4Chair of Natural Product Chemistry, Friedrich-Schiller-University Jena, Jena, Germany
5Microbiology and Molecular Biology, Friedrich-Schiller-University Jena, Jena, Germany

In environmental microbial consortia natural products, also known as secondary metabolites (SMs), play a pivotal role acting as infochemicals or as antimicrobials for the defense against competitors (1). Several secondary metabolites exhibit pharmacological properties revealing their particular importance in the medical field (2). Recently, we discovered that the model organism Aspergillus nidulans specifically interacts with the soil-dwelling bacterium Streptomyces rapamycinicus and its closely related Streptomyces iranensis (3). As a consequence, the silent orsellinic acid (ors) gene cluster is activated in the fungus, leading to the formation of orsellinic acid, lecanoric acid and derivatives thereof. Continuation of this work led to the discovery that the co-cultivation with S. rapamycinicus leads to a re-programming of the histone acetyltransferase GcnE-containing SAGA/ADA complex of A. nidulans (4). Consequently, the histone H3 amino acids K9 and K14 were specifically acetylated at distinct natural product genes (5). The transcription factor BasR was identified as a novel regulator of secondary metabolism during the bacterial-fungal interaction by performing a genome-wide chromatin immunoprecipitation (ChIP) analysis (6). Here, we present a molecular characterisation of the novel regulator BasR in Aspergillus nidulans and its impact on the regulation of secondary metabolism during the interaction with the streptomycete.

(1) Spiteller, (2015) Nat. Prod. Rep., (2) Brakhage, (2013) Nature, (3) Schroeckh et al., (2009) PNAS, (4) Nützmann et al., (2011) PNAS, (5) Nützmann et al., (2013) AEM, (6) Fischer et al., in preparation