Collaborative Research: Emergence of terpene cyclization in animals

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Chemical interactions between organisms represent a key form of communication in nature and is mediated by diverse arrays of small molecules. These molecules or chemical cues serve critical roles in maintaining and driving species diversity and ecosystem functions. Using interdisciplinary methods, the team of investigators explore the question of how chemical compounds emerge and adopt biological functions with a specific focus on understanding the emergence of terpenes - a major family of molecules used by insects to ward off enemies and pathogens, search for food, and attract or seek out mates. Integrating computational modeling and molecular modifications, the project reconstructs the evolution of enzymes that are central to the generation of terpene chemical diversity in insects. Through their study, the investigators will develop an integrated empirical and theoretical platform that will serve as a blueprint for tracing the evolution of various protein families. The project has broader societal and educational impacts, including potential generation of target enzyme products and gene variants for industrial applications and translation of research results into a visual installation, which will be accessible to the general public through theaters at Virginia Tech and the Science Museum of Western Virginia. Terpenes constitute a large class of mostly cyclic molecules with major roles in chemical interactions of organisms. However, the emergence of enzymatic functions responsible for the cyclization and diversity of terpenes in animals has remained elusive. The research team will apply a combination of computational and experimental methods to define key enzymatic adaptations underlying terpene diversity in insects - the most species-rich lineage of animals. Specifically, the project defines modifications that activate terpene cyclase (TPS) enzymatic function in isoprenyl diphosphate synthases (IDS), enzymes involved in core terpene metabolism. Investigators will identify and functionally characterize terpene cyclase enzymes in diverse insect taxa to assess adaptive changes corresponding to the evolution of these enzymes in insects. The functional data will be combined with protein structural analysis to generate models that pinpoint amino acid residue networks, which trigger the emergence of TPS activities on IDS templates. Network models will be used to construct synthetic enzyme libraries and help characterize mutational pathways that underlie terpene cyclization. Investigators will also use data from the study to develop integrated biophysical models of enzyme evolutionary dynamics that quantitatively describe fundamental transitions of enzyme function in the emergence of terpene diversity. Cumulatively, the insights from this interdisciplinary project will lead to an improved understanding of the biophysical principles behind major expansions of enzymatic and chemical diversity in nature.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.