PlantSynBio: Integrate Natural Product Biosynthesis into the Global Metabolic Network

本项目旨在确定天然产物的生物合成如何与全球代谢网络相互联系，以毛地黄植物的心糖苷生物合成为例。该项目对开发农业抗逆性作物以及推进可用于改善人类健康的天然产品的开发和生物制造具有更广泛的意义。鉴于公众对毛地黄药用的了解，这项研究将通过为每个年龄组量身定制的活动，吸引公众，特别是STEM中代表性不足的女性。该项目将通过美国大学妇女协会在布法罗成立的年度活动建立一个实践研讨会。这项研究还将每年通过路易斯·斯托克斯少数民族参与联盟暑期项目招收一名本科生。该项目将支持培养一名博士生，使其不仅成为一名优秀的研究人员，而且成为一名热心的STEM倡导者。与大多数具有线性结构的中心代谢途径不同，许多植物天然产物途径是高度网络化的。一个突出的例子是毛地黄植物中心苷的生物合成。该项目的总体目标是阐明心脏糖苷的生物合成如何与全球代谢网络相互联系。初步结果表明，毛地黄植物在初级代谢过程中通过与其他类固醇相互交织的代谢网络合成心糖苷。该项目将通过使用计算和实验方法将心糖苷生物合成整合到全球代谢网络中来验证这一假设。该项目有望揭示碳和电子如何从中央代谢流向心脏糖苷的定量见解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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, especially underrepresented women in STEM, through activities tailored for each age group. This project will establish a hands-on workshop through the annual event founded by the American Association of University Women in Buffalo. This research will also recruit one undergraduate student each year through the Louis Stokes Alliance for Minority Participation summer program. This project will 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.