Plants synthesize an immense number of bioactive small molecules with useful therapeutic properties. These molecules are responsible for the beneficial effects of traditional plant medicines that have been used for thousands of years, and plant-derived compounds are still used as pharmaceuticals to treat numerous medical conditions, including pain, cancer, inflammation, and neurological disease. However, our ability to utilize these molecules is challenged by the difficulty in sourcing them from medicinal plants, which are difficult to cultivate and often threatened by overharvest from native habitats. Although metabolic engineering of plant-based pharmaceuticals could alleviate these issues, this approach is prevented by our limited understanding of the underlying biosynthetic machinery, which has historically been difficult to identify in plants. By combining medicinal plant metabolomics and transcriptomics with rapid enzyme testing in a plant host, I have helped to accelerate the rate at which we can identify and characterize biosynthetic genes and metabolic pathways for pharmaceutical plant molecules. This has allowed me to quickly elucidate a near-complete pathway for the neuroactive molecule huperzine A, and I have further used this strategy to discover a full biosynthetic pathway for the FDA-approved, anti-inflammatory drug colchicine. These efforts pave the way for the engineered production of plant-derived pharmaceutical molecules within biological systems, and demonstrate our rapidly increasing ability to harness the complexity of plant chemistry for developing new medicines and improving agricultural traits.
View the recording of this seminar here.