Mining the fungal biodiversity for novel natural product discovery

The fungal kingdom is a well-known source of useful compounds called natural products or secondary metabolites (SMs). Their diverse biological activities are of great interest for medicine, industry and agriculture. Analyses of fungal genomes have revealed a discrepancy between the few known SMs produced by a given species relative to the many biosynthetic pathways encoded by their genomes. Despite the pivotal role in modern medicine of fungal antibacterials (e.g. penicillin) and immunosuppressive compounds (cyclosporine), the chemical diversity within the fungal kingdom has remained underexploited. This can partly be explained by the difficulty in finding conditions conducive to SM production. The Westerdijk Fungal Biodiversity Institute maintains the world largest collection of fungal species and represent a unique resource for the discovery of novel SMs. The newly established Fungal Natural Products group is harnessing this biodiversity using microbiological, computational and synthetic biological approaches. By integrating these complementary methods, we are able to discover novel SMs and identify their corresponding biosynthetic gene clusters, the first step towards engineering of biosynthetic pathways. This research is performed within the Utrecht Fungal Network, a collaborative effort between the Westerdijk Institute, Utrecht University, University Medical Centre Utrecht and the Hubrecht Institute to mine the fungal biodiversity.