Decoding the chromatin dynamics of fungal BGCs

As human populations increase while arable land area decreases limited food resources will become a global challenge in the near future. Plant diseases caused by fungi represent the most important threat to the global food supply, yet finding sustainable ways to limit diseases and food spoilage caused by mycotoxins (so-called secondary metabolites, SMs) remains a key challenge. Next to this, fungi are also known to produce highly effective antibiotics. As antibiotic resistance is one of the biggest threats to global health, discovery of new antibiotics is urgently needed. In both regards, knowledge on the determinants that govern SM biosynthesis is a key challenge in this field of study. Limitations to exploit the full genetic potential of SM-producing fungi arise from the fact that only a fraction of SMs is produced under standard laboratory conditions. This proposal aims at overcoming these limitations by exploring SM gene regulation at the level of chromatin. Removal of heterochromatin (H3K9me3 and H3K27me3) impacts SM gene expression in fusaria. Yet, it remains unknown how this is orchestrated at the molecular level, especially since H3K9me3 is absent from de-regulated SM genes. I propose to investigate components involved in the establishment, maintenance and removal of heterochromatin in the genus Fusarium, and analyze their interplay. Moreover, I want to explore the full chemical potential of the fungus by using heterochromatin-deficient strains. It is currently also unknown how silenced genes are re-activated to allow for gene expression in fungi. I propose to analyze possible candidate genes, to identify involved histone demethylases. Obtained knowledge will thus provide foundational knowledge to advance the understanding of epigenetic mechanisms ruling fungal life traits, but also for novel drug-discovery strategies