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

昆虫病原真菌(EPF)是感染和杀死昆虫的真菌。一些EPF已被开发为商业生物杀虫剂，由于合成农药对环境的影响、法规的变化(例如欧盟指令2009/128/EC)、杀虫剂耐药性以及公众对可持续生产食品日益增长的需求，EPF的使用变得越来越不重要。现有对EPF次生代谢物的研究主要集中在鉴定具有药用价值的化合物上，如从膨胀弯孢霉中分离出环孢菌素。然而，这项研究一直受到阻碍，因为EPF代谢物在实验室条件下是瞬时产生的，数量很少，或者根本不产生。目标：开发新的液体发酵方法，以复制昆虫宿主的生化条件。分析与现有栽培方法相比，次生代谢物分布的差异。分离和结构阐明与发病相关的代谢物，使我们了解作用方式和生物合成途径。利用更大规模的液体EPF培养，利用一种以检测为主导的方法，对具有药物或害虫防治特性的新化合物进行生物展望。对一种或多种选择的二解物进行基因组测序，以描述病原体基因组内的总代谢物多样性。对发酵罐培养物进行RNA序列分析，以确定负责次生代谢物产生的基因。使用可公开获得的EPF基因组的比较基因组学来确定关键代谢物基因簇的保守性，并具有潜在的虫害防治能力。

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.