PlantSynBio: Deciphering the effects of structural variation in specialized metabolites on plant-insect interactions

Insect herbivores cause losses for global agricultural productivity that are estimated at twenty to thirty percent of annual agricultural produce in the USA. Economic and ecological costs of wide-spread chemical pesticide use and the resultant emergence of pesticide-resistance underscore the urgent need to research safe and sustainable crop defense strategies. Plants produce hundreds of thousands of specialized metabolites to interact with the environment around them. Humans have adopted and modified these clade-specific compounds as medicines, food additives and natural insecticides over thousands of years. Despite our knowledge of the activities and value of many of these products, addressing how the changing composition of lineage-specific specialized metabolites affects plant-biotic interactions remains a great challenge. Solanaceae acylsugars present a promising system to lay the groundwork for this. By critically exploring the anti-herbivory structure-activity relationship of acylsugars in planta, this project will reveal potent structures with enhanced pest resistance, pinpoint molecular mechanisms underlying the biodiversity of acylsugars, and suggest nature-guided solutions for metabolic engineering and synthetic biology to create safe and sustainable plant defense metabolites powerful against current and future pests. The outcome of this project will provide knowledge of agricultural interests and advance plant synthetic biology and chemical ecology. This research also directly advances the fields of NSF strategic priorities, including biotechnology and artificial intellegence: by characterizing novel gene targets and pathway engineering strategies, this project develops a biotechnology framework for modifying complicated specialized metabolites in planta. Moreover, the extensive sequence datasets generated through our biochemical and bioinformatic analyses serve as fundamental resources for AI-powered predictive protein structure-function relationships models. To achieve the above goals, this project will employ plant synthetic biology and metabolomics to decipher structural effects of Solanaceae acylsugars on plant-insect interaction. We will create diverse chemotypes in isogenic backgrounds for direct and unequivocal functional analysis of an array of structurally diverse acylsugars (Aims 1 and 2). Simultaneously, we will establish a framework of knowledge – largely via course-based undergraduate student experiential learning – for constructing the complete acylsugar chemical phylogeny in an isogenic background for decoding the chemical ‘arms race’ between plants and their biotic stressors (Aim 3). The results of the proposed experiments will expand our knowledge of the biochemical mechanisms by which plants survive biotic stressors, directly informing breeding and molecular engineering strategies to improve crop plants resistance. The outcome of this project will also serve as a foundation for addressing the emergence and maintenance of natural chemical diversity in other non-model systems. The project will train a postdoc, a graduate student, a bachelor-level technician, and provide college-level system and synthetic biology education to develop a globally competitive workforce in this rising field. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. NSF Award ID: 2532196 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Yann-Ru Lou | Institution: University of California-Davis, DAVIS, CA | Award Amount: $1,252,158 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2532196 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2532196.html