(553e) Microbial Conversion of Vegetable Oils into Omega-3 Oils

Omega-3 fatty acids, including eicosapentaenoic acid (EPA C20:5) and docosahexaenoic acid (DHA C22:6), are long-chain unsaturated fatty acid with great benefits in heart health, improving immune function, and cognition development. Recent research also shows that omega-3 fatty acids can help patients recover from COVID-19. However, human body cannot directly synthesize omega-3 fatty acids, people need to obtain these long-chain unsaturated fatty acids from their daily diet. The traditional source of DHA and EPA are obtained from fish oils via an extraction process, whose supply is subject to a big challenge due to the uncertainty caused by overfishing and the concern of contaminations in ocean. Biomanufacturing of omega-3 fatty acids by microorganisms are considered a more sustainable and green approach to produce healthier and higher-quality omega-3 fatty acids. Recently, DuPont has developed a technology that uses metabolically engineered Yarrowia lipolytica to produce omega-3 EPA from glucose. However, the manufacturing cost needs to be further reduced due to the low conversion yield. Here we report a novel strategy for high-yield production of omega-3 fatty acids from vegetable oils. The metabolic pathways and fermentation strategies for direct conversion of canola oil into omega-3 EPA are investigated and optimized, which include (1) acceleration of oil substrate uptake by increasing lipase activity, (2) enhancing intracellular omega-3 EPA formation and accumulation via pathway engineering and optimization in fatty acid synthesis and metabolism, (3) minimizing lipid leaking from the yeast cells, and (4) fermentation engineering to avoid limitations in mass transfer and mixing. We have demonstrated more than 50% improvements in omega-3 EPA production when the canola oil is used to partially or completely replace glucose as the carbon source. To our best knowledge, this is the first research reporting a direct and efficient microbial conversion of a plant oil into a much more valuable omega-3 oil at significantly higher titer and yield.

Key words: Y. lipolytica, metabolic engineering, fermentation engineering, omega-3 fatty acids, eicosapentaenoic acid (EPA), vegetable oil.