Mining the untapped chemical potential of entomopathogenic fungi for sustainable agriculture and human health.

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Entomopathogenic fungi (EPF) are fungi that infect and kill insects. Some EPF havebeen developed as commercial biopesticides, the use of which has grown inimportance in response to the environmental impact of synthetic pesticides, changesin regulations (e.g. EU Directive 2009/128/EC), insecticide resistance and growingpublic demand for sustainably produced food. Existing research on the secondarymetabolites of EPF has focused on identifying compounds with medicinal benefits e.g.cyclosporine from Tolypocladium inflatum. However, this research has been hindereddue to EPF metabolites being produced transiently, in low quantities or not at all underlaboratory conditions. Goals: Develop new liquid fermentation methodologies toreplicate the biochemical conditions in insect hosts. Analyse differences in secondarymetabolite profile, compared to existing cultivation methods. Isolation and structuralelucidation of metabolites associated with pathogenesis, informing our knowledge ofthe mode of action and biosynthetic pathways. Using the larger scale liquid EPFcultures, bioprospect for novel compounds with drug or pest control properties usingan assay led methodology. Perform genome sequencing of one or more selectedisolates to profile total metabolite diversity within the pathogen genome. PerformRNA seq analysis of fermenter cultures to identify genes responsible for secondarymetabolite production. Use comparative genomics with publicly available EPFgenomes to identify conservation of key metabolite gene clusters with potential forpest control.