Combined Fermentation-based Biosynthesis and Whole-Animal Screening Platform for Biobased Nematicide Discovery & Commercialization

Plant parasitic nematodes cause over $125 billion USD a year in food production losses, or over 12% of all crops. Regulatory changes are resulting in fewer options for nematode control for farmers and requiring that new products be more sustainable in use. Optimized through evolutionary processes for biological activity, natural products (NPs) are a rich source of bioactive molecules that are biodegradable and safer for farmers, consumers, and the environment than conventional synthetic pesticides. Biopesticide discovery based on NPs has been limited by many obstacles, including sourcing enough material for testing and commercialization. Fortunately, the genomics revolution has enabled the development of microbial production processes for NPs using synthetic biology and metabolic engineering, providing new hope for the discovery of novel NP-derived compounds as biopesticide candidates.The project involves the creation of novel biochemical pathways in microbes. These new pathways will createnatural products that are found in nature, as well as novel compounds that are inspired by and derived from these complex natural products. Since these natural products will be created using polymerization, cyclization, and oxygenation chemistries, they will have significant bioactivity potential and will establisha scalable compound library generation platform with a high chance of creating new pharmaceutical products and pesticides to protect against roundworm diseases and infections. By combining these chemistries in a cell and producing the compounds via fermentation, we will develop both a screening method and a production method in one step, enabling the economical production and commercialization of any lead compounds with useful activities.The project deliverables will be:(1) a novel and efficientscreening platform for drug and agricultural chemical discovery;(2) an extensive library of new natural products with significant potential to be commercialized;(3) a novel nematicide that will be used to protect crops and improve farming yieldfor USfarmers, both in large-acre and high value crop applications.