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。一些著名的植物衍生小分子包括尼古丁、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尚不清楚。这限制了这些活性药物分子的来源，只能通过植物的收获和提取。这个项目将研究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生物体内产品的生产。这种方法还有助于揭示合成途径的细节。此外，这个研究项目将追求教育目标。首先是通过为本科女性提供研究机会，增加追求STEM职业道路的女学生数量。二是为附近高中和社区大学的学生提供暑期研究机会，激励下一代科学家和工程师。以微生物生产为平台研究植物次生代谢的可行性和效率将得到评价。甾体内酯（SLs）是一类植物激素，将作为模型化合物进行研究。SLs对植物生长发育至关重要。它们在自然界的丰度通常极低。假定的SL生物合成途径的基因将被克隆到微生物系统中并表达。将追求三个具体目标。首先，将对最近建立的SL生产微生物群落进行优化，以生产SL。然后，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。该项目将在以下方面迈出重要一步：(1)推进对植物特殊代谢的基础认识，(2)促进农业和制药领域新植物化学物质的发现和利用，以及(3)发展具有更高生产力和复原力的下一代精准农业。该项目还可以为在谷类作物中培养抗斯曲加菌的能力以防止作物损失提供基础。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。

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.