PlantSynBio: Integrate Natural Product Biosynthesis into the Global Metabolic Network

This project aims to identify how natural product biosynthesis interconnects with the global metabolic network, using cardiac glycoside biosynthesis in the foxglove plant as an example. This project has broader implications for developing stress-resistant crops in agriculture and advancing the development and biomanufacturing of natural products that can be used to improve human health. Given the public knowledge of the foxglove’s medicinal use, this research will be leveraged to engage the public through activities tailored for each age group. This project will also support the training of one Ph.D. student not only as an outstanding researcher but also as an enthusiastic STEM advocate. Unlike most central metabolic pathways with a linear architecture, many plant natural product pathways are highly networked. One prominent example is the biosynthesis of cardiac glycosides in foxglove plants. The overall objective of this project is to elucidate how the biosynthesis of cardiac glycosides interconnects with the global metabolic network. Preliminary results led to the hypothesis that the foxglove plant synthesizes cardiac glycosides through a metabolic network intertwined with other steroids in the primary metabolism. This project will test this hypothesis by integrating cardiac glycoside biosynthesis into the global metabolic network using both computational and experimental approaches. This project is expected to reveal quantitative insights into how carbon and electrons flow from the central metabolism to cardiac glycosides. 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.