S124: Production of eicosapentaenoic acid from Yarrowia lipolytica

Omega-3 fatty acids are essential nutrients in the diets of humans and animals.  The current major source of omega-3 fatty acids is fish oil.  However, concerns over the quality and sustainability of the fish oil supply have generated interest in supplying omega-3 fatty acids from alternative sources.  We developed a clean and sustainable source of omega-3 fatty acids by fermentation for commercial production, using a metabolically engineered strain of the oleaginous yeast Yarrowia lipolytica.  The yeast triacylglyceride oil has a unique fatty acid profile with greater than 55% as EPA, and less than 8% as saturated fatty acid. The metabolic engineering of Y. lipolytica provides a platform technology for producing omega-3 or omega-6 fatty acids of tailored compositions, for applications in nutritional supplements, functional foods, infant foods, pharmaceuticals, and animal feeds.

We also report the identification of regulatory proteins for lipid metabolism in Y. lipolytica. When the Y. lipolytica SNF1 gene was deleted, cells accumulate lipid constitutively. In Saccharomyces cerevisiae, the Snf1 kinase signal transduction pathway is the key regulator of central carbon metabolism and is responsible for glucose repression, but little is known about its regulatory role in lipid metabolism. Deletion and overexpression analyses as well as microarray analysis confirmed that the components of the Yarrowia Snf1 pathway are important for lipid accumulation. This work demonstrated that Y. lipolytica is not only an excellent organism for sustainable production of vegetarian Omega-3 fatty acids but also a model system to study/ understand the regulation of lipid metabolism.