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

美国每年生产2000多万吨植物油和动物脂肪。用于食品和饲料应用，它们产生的经济价值很低或有限。食品生产过程中浪费的植物油和脂肪会对环境造成负面影响。该项目旨在开发一种酵母，将油脂转化为一系列高附加值产品。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，该项目可以使用酵母创造出对环境影响最小、改善人类健康的产品。高中教师将在实验室接受培训，本科生和研究生也是如此。目前对德州聋人学校和当地一所K-5小学的外联活动将得到加强，招募人数不足的少数族裔和妇女参加STEM培训的努力也将扩大。总体而言，该项目将支持发展一支为在不断增长的生物经济行业中发挥领导作用而做好准备的劳动力。油脂酵母将经过代谢工程，将油脂转化为高价值产品。细胞工程和生物反应工程研究将整合在这个项目中，建立这个生物制造平台。首先，酵母将在代谢和生理上进行改造，以促进细胞外底物的吸收和细胞内脂肪酸的生物运输。其次，通过修饰细胞转运蛋白，将增强对脂肪酸底物的摄取。第三，将建立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、类胡萝卜素和其他产品。第四，在生物过程方面，通过使用多相(气体、石油、水)计算流体动力学(CFD)模型，将减少疏水底物在水介质中不溶于细胞外的油/脂肪/脂肪酸在生物反应器中的传质限制。最终，将建立一个通用的生物反应器模型来描述油脂的胞外质量转移和脂肪酸在细胞内的生物转化为每一种特定的高价值产品的过程。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。

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.