SYM-23-04: Bioplatforms Australia Award Lecture

Genome mining of cryptic metabolites in fungi: opportunities for small molecule discovery and advancing host–microbe interactions

YH Chooi

School of Chemistry and Biochemistry, University of Western Australia

Fungi produce a large arsenal of secondary metabolites that have important bio-ecological functions, such as competing for nutrients, self-defence, and as virulence factors (pathogenic fungi). Many of these secondary metabolites serve as drugs for human, including penicillin and lovastatin. Fungal genome sequencing revealed a large number of cryptic secondary metabolite gene clusters suggesting that we have only discovered a small portion of the metabolites encoded in the fungal genomes. This presents new prospects for discovery of novel bioactive molecules but at the same time highlights our paucity of knowledge about the biological roles of fungal secondary metabolites, especially in the context of fungal diseases of plants and humans. Guided by established biosynthetic logic, we employ a combination of functional genomics, synthetic biology, biochemistry and chemical ecology to uncover the cryptic metabolites from fungi and their biological functions. Some examples from our past and recent studies will be presented, including the discovery of a novel immunosuppressive compound neosartoricin from human pathogenic fungi as well as antigerminative and phytotoxic compounds from plant pathogenic fungi.