Decoding chromatin dynamics of fungal biosynthetic gene clusters

As human populations increase while arable land area decreases limited food resources will become a global challenge in the near future. This issue becomes even more clear and urgent in times, in which climate change and geopolitical crises endanger the global food supply. 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 remains a key challenge. To date there is no existing cropping strategy that is fully effective in limiting mycotoxin contaminations and guarantees compliance with official limits (set by EC regulation number 1881/2006). On top of that, published fungal genomes illustrate the enormous genetic capacity to produce hitherto unknown, potentially toxic compounds (so-called secondary metabolites, SMs) not even considered yet1. This is further underlined by the fact that fungal communities are rapidly adapting to changing environmental conditions e.g. mycotoxin occurrence is affected by weather fluctuations and climate change. Next to this, fungi are also known to produce highly effective antibiotics (e.g. penicillin). As antibiotic resistance is one of the biggest threats to global health, food security, and development of our time, discovery of new antibiotics is urgently needed. Without immediate action, we are heading for a post-antibiotic era, in which common infections and minor injuries can once again become life threatening. In both regards, knowledge on the determinants that govern fungal 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 these compounds is produced under standard laboratory conditions. Over the past years, chromatin structure, as determined by changes in histone marks, emerged as a key player in regulating SM gene expression. A breakthrough was the finding that a large proportion of SM genes is silenced by facultative heterochromatin in the genus Fusarium, one of the most economically important fungal genera in the world. Using strains deficient in facultative heterochromatin will be key to fully exploit the chemical potential of filamentous fungi.