Collaborative Research: A New Yeast Biomanufacturing Platform for Making High-value Products from Oils and Fats

美国每年生产超过2000万吨的植物油和动物脂肪。用于食品和饲料应用，它们产生低或有限的经济价值。在粮食生产过程中浪费的植物油和脂肪对环境产生负面影响。本项目旨在开发一种酵母，将油脂转化为一系列高价值产品。这些产品可能包括omega-3脂肪酸、类胡萝卜素和蜡酯。如果成功的话，这个项目可以用酵母制造出对环境影响最小的产品，改善人类健康。高中教师、本科生和研究生将在实验室接受培训。目前对德克萨斯聋人学校和当地一所K-5小学的外展活动将得到加强，招募代表性不足的少数民族和妇女参加STEM培训的努力也将得到加强。总体而言，该项目将支持培养一支为不断发展的生物经济行业的领导人才。产油酵母解脂耶氏酵母将通过代谢工程将油和脂肪转化为高价值产品。本项目将结合细胞工程和生物反应工程研究，建立生物制造平台。首先，酵母将在代谢和生理上进行工程改造，以促进细胞外底物的吸收和细胞内脂肪酸的生物转化。其次，脂肪酸底物的摄取将通过修饰细胞转运体而增强。第三，创造和优化生物合成途径，将细胞内脂肪酸转化为omega-3脂肪酸、蜡酯、类胡萝卜素等产品。第四，在生物过程方面，通过使用多相（气、油、水）计算流体动力学（CFD）模型，将减少生物反应器中由疏水底物在水介质中的不溶性引起的细胞外油/脂肪/脂肪酸的传质限制。最终，将建立一个通用的生物反应器模型，以描述油/脂肪的细胞外质量传递和脂肪酸在细胞内生物转化为每种特定高价值产品的过程。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。

The United States produces more than 20 million tons of plant oils and animal fats every year. Used for food and feed applications, they generate low or limited economic value. The plant oils and fats wasted during food production negatively impact the environment. This project aims to develop a yeast to convert oils and fats into a series of high-value products. These products might include omega-3 fatty acids, carotenoids, and wax esters. If successful, this project could use yeast to create products that improve human health with minimal environmental impact. High school teachers will be trained in the lab, as will undergraduates and graduate students. Current outreach activities to the Texas School for the Deaf and a local K-5 elementary school will be augmented, as will efforts to recruit underrepresented minorities and women to pursue STEM training. Overall, the project will support the development of a workforce prepared for leadership in the growing bioeconomy industry.The oleaginous yeast Yarrowia lipolytica will be metabolically engineered to convert oils and fats into high-value products. Both cellular engineering and bioreaction engineering research will be integrated in this project to establish this biomanufacturing platform. First, the yeast will be engineered both metabolically and physiologically to facilitate the uptake of extracellular substrate and the bioconvesion of intracellular fatty acids. Second, the uptake of fatty acid substrates will be enhanced through modifying cellular transporters. Third, biosynthesis pathways will be created and optimized to convert the intracellular fatty acids into omega-3 fatty acids, wax esters, carotenoids, and other products. Forth, on the bioprocess side, mass transfer limitations of extracellular oils/fats/fatty acids in a bioreactor caused by the insolubility of the hydrophobic substrates in aqueous medium will be reduced through the use of a multi-phase (gas, oil, aqueous) computational fluid dynamics (CFD) model. Ultimately, a general bioreactor model will be built to describe processes for both extracellular mass transfer of oils/fats and the intracellular bioconversion of fatty acids into each specific high-value product.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.