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

Entomopathogenic fungi (EPF) are fungi that infect and kill insects. Some EPF have
been developed as commercial biopesticides, the use of which has grown in
importance in response to the environmental impact of synthetic pesticides, changes
in regulations (e.g. EU Directive 2009/128/EC), insecticide resistance and growing
public demand for sustainably produced food. Existing research on the secondary
metabolites of EPF has focused on identifying compounds with medicinal benefits e.g.
cyclosporine from Tolypocladium inflatum. However, this research has been hindered
due to EPF metabolites being produced transiently, in low quantities or not at all under
laboratory conditions. Goals: Develop new liquid fermentation methodologies to
replicate the biochemical conditions in insect hosts. Analyse differences in secondary
metabolite profile, compared to existing cultivation methods. Isolation and structural
elucidation of metabolites associated with pathogenesis, informing our knowledge of
the mode of action and biosynthetic pathways. Using the larger scale liquid EPF
cultures, bioprospect for novel compounds with drug or pest control properties using
an assay led methodology. Perform genome sequencing of one or more selected
isolates to profile total metabolite diversity within the pathogen genome. Perform
RNA seq analysis of fermenter cultures to identify genes responsible for secondary
metabolite production. Use comparative genomics with publicly available EPF
genomes to identify conservation of key metabolite gene clusters with potential for
pest control.