Thiol-based redox switch in plant flavonoid biosynthesis

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The Chemistry of Life Processes Program in the Chemistry Division funds this award. Dr. Jing-Ke Weng from the Whitehead Institute for Biomedical Research investigates the impact of a chemical reactions with oxygen in regulating a plant enzyme. All land plants produce a class of molecules called flavonoids, using the enzyme known as chalcone synthase. Flavonoids are important for plants to survive on land and play many roles such as protection against ultraviolet light, defense against herbivores, and attraction of pollinators. Using high resolution techniques for the determination of structure, chalcone synthase was observed to have evolved a regulatory switch that affects its activity when it reacts with oxygen. By comparing chalcone synthase from a variety of plants such as simple land plants to flowering plants, this research helps characterize how flavonoid biosynthesis has evolved to help plants adapt to life in a wide variety of terrestrial habitats. This knowledge has the potential to improve plant traits in the future. This project allows graduate students to acquire hands-on training in multidisciplinary cutting-edge techniques. This project also integrates middle-school and high-school outreach programs to introduce students to plant physiology and chemistry. Oxidation of the cysteinyl side chain in proteins occurs widely in all living organisms, often as a result of increased levels of reactive oxygen species (ROS). The goal of this research is to gain a mechanistic understanding of how the activity of chalcone synthase (CHS), the first committed enzyme in plant flavonoid biosynthesis, is controlled by oxidative inactivation of its catalytic cysteine at both the enzyme and systems levels. CHS orthologs from diverse land plant lineages are characterized in vitro using X-ray crystallography and enzyme activity assays to examine how the redox potential of the catalytic cysteine is impacted by nearby amino acid differences between orthologs. In vivo studies involving metabolic tracing and proteomics on transgenic Arabidopsis thaliana expressing different CHS orthologs and subjected to various oxidative stress conditions examine the impact of CHS oxidation on flavonoid biosynthesis, and provide insight into its functional impact on the evolution of land plants. Because CHSs are homologous to, and evolutionarily derived from, the beta-ketoacyl-(acyl-carrier-protein) synthases, the proposed research has far-reaching impact for understanding how fatty acid biosynthesis may be influenced by fluctuating cellular redox status, which is an underexplored research topic relevant to diverse disciplines, e.g. oil production in seed crops under stress conditions.