CAREER: Using Microbial Bioproduction Platform to Elucidate Phytochemical Biosynthesis - Strigolactone as An Example

植物产生的小分子对健康有多种影响。一些众所周知的植物来源的小分子包括尼古丁、咖啡因、精油、阿司匹林、洋地黄和香豆素。这些分子的生物合成还没有被很好地理解。这将这些活性药物分子的来源限制在植物收获和提取上。这个项目将探索一种制造它们的新方法。这将涉及将潜在的植物途径基因转移到酵母中，并评估该有机体中产品的生产。这种方法还有助于揭示合成途径的细节。此外，这项研究项目将追求教育目标。第一是通过为本科生提供研究机会，增加从事STEM职业道路的女学生的数量。第二是通过为附近高中和社区大学的学生提供暑期研究机会来激励下一代科学家和工程师。将评估利用微生物生产作为阐明植物次生代谢的平台的可行性和效率。植物激素类化合物Strigolactones(SLS)将成为研究的模型化合物。SLS对植物的生长发育是必不可少的。它们通常在自然界中表现出极低的丰度。可能的SL生物合成途径的基因将被克隆到微生物系统中并进行表达。将追求三个具体目标。首先，最近建立的生产SL的微生物联合体将针对SL生产进行优化。然后，我们将阐明谷类作物，特别是高粱和玉米中SL生物合成的机制。最后，将努力建立单细胞SL生物生产。该项目可向以下方向迈出重要一步：(1)促进对植物专门化代谢的基础了解；(2)促进用于农业和医药应用的新型植物化学物质的发现和利用；(3)发展生产率和复原力更高的下一代精准农业。该项目还可以为开发谷类作物的抗旱性以防止作物损失提供基础。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Plants produce small molecules with a variety of health effects. Some well-known plant-derived small molecules include nicotine, caffeine, essential oils, aspirin, digitalis, and coumarin. The biological synthesis of these molecules is not well-understood. This limits the source of these active pharmaceutical molecules to plant harvest and extraction. This project will investigate a new approach for their manufacture. This will involve transferring potential plant pathway genes into yeast and evaluating production of the products in that organism. This approach also helps to uncover the details of the synthetic pathways. In addition, this research project will pursue educational goals. The first is to increase the number of female students pursuing STEM career paths by offering undergraduate women research opportunities. The second is to inspire the next generation of scientists and engineers by offering summer research opportunities to students from nearby high schools and community colleges. The feasibility and efficiency of using microbial bioproduction as a platform to elucidate plant secondary metabolism will be evaluated. Strigolactones (SLs), a class of plant hormones, will be the model compounds studied. SLs are essential for plant growth and development. They normally exhibit extremely low abundance in nature. The genes for the putative SL biosynthetic pathway will be cloned into microbial systems and expressed. Three specific objectives will be pursued. First, the recently established SL-producing microbial consortia will be optimized for SL production. Then, the mechanisms driving SL biosynthesis in cereal crops, specifically sorghum and maize, will be elucidated. Finally, efforts will be made to establish single-cell SL bioproduction. This project could provide a significant step towards (1) advancing the foundational understanding of plant specialized metabolism, (2) promoting the discovery and utilization of novel phytochemicals for agricultural and pharmaceutical applications, and (3) developing next-generation precision agriculture with enhanced productivity and resilience. The project could also provide the foundation to develop Striga-resistance in cereal crops to prevent crop loss.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.