PlantSynBio: Integrate Natural Product Biosynthesis into the Global Metabolic Network

该项目旨在确定天然产物生物合成如何与全球代谢网络相互联系，以毛地黄植物中的强心苷生物合成为例。该项目对开发农业中的抗逆作物以及促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影响。鉴于公众对毛地黄的药用知识，这项研究将通过为每个年龄组量身定制的活动，吸引公众，特别是在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举办的年度活动，建立一个实践讲习班。这项研究还将通过路易斯·斯托克斯少数民族参与暑期项目联盟每年招募一名本科生。该项目将支持培养一名博士。学生不仅是杰出的研究人员，而且是热情的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强心苷的生物合成。该项目的总体目标是阐明强心苷的生物合成如何与全球代谢网络相互联系。初步结果导致了这样的假设，即毛地黄植物通过与初级代谢中的其他类固醇交织的代谢网络合成强心苷。该项目将通过使用计算和实验方法将强心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枢代谢流向强心苷的定量见解。该奖项反映了NSF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.