Novel regulator induces biosynthesis of cryptic natural products in the fungus Aspergillus sydowii


Maria Cristina Stroe 1,5 Tina Netzker 1 Vito Valiante 3 Kirstin Scherlach 2 Volker Schroeckh 1 Christian Hertweck 2,4 Axel A. Brakhage 1,5
1Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany
2Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany
3Research Group Biobricks of Microbial Natural Product Synthetases, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany
4Natural Product Chemistry, Friedrich Schiller University Jena (FSU), Jena, Germany
5Institute of Microbiology, Friedrich Schiller University Jena (FSU), Jena, Germany

Natural products are low-molecular mass compounds with diverse chemical structures and important pharmacological activities, ranging from antibiotics to cholesterol-lowering agents (1). Filamentous fungi are well-known producers of such molecules, and recent advances in sequencing and genome mining have revealed that the biosynthetic potential of fungi is far greater than the number of currently identified compounds (2). This finding prompted the development of new methods to activate the biosynthesis of cryptic natural products. One successful approach is to simulate natural environmental conditions through co-cultivation of microorganisms (3). We previously showed that in a mixed fermentation, the bacterium Streptomyces rapamycinicus leads to the activation of the silent orsellinic acid (ors) gene cluster of the fungus Aspergillus nidulans (4). The metabolite production was further shown to be dependent on a novel regulator termed BasR (5), which is induced during the bacterial-fungal interaction. Here, we show that this transcription factor is responsible for the activation of the ors cluster in the related fungus Aspergillus sydowii, where its induced expression is able to activate the fungal secondary metabolism and triggers the biosynthesis of cryptic compounds.

(1) Brakhage (2013) Nature, (2) Macheleidt et al., (2016) Annu Rev Genet, (3) Netzker et al., (2015) Front Microbiol, (4) Schroeckh et al., (2009) PNAS, (6) Fischer et al., in preparation