S3: Production of omega-3 fatty acids from Yarrowia lipolytica: factors affecting lipid accumulation

EPA and DHA omega-3 fatty acids are essential nutrients in the diets of humans and animals. The current major source of EPA and DHA 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 EPA by fermentation for commercial production, using a metabolically engineered strain of the oleaginous yeast Yarrowia lipolytica. Disruption of pex10 function and overexpression of acyltransferease have major effect on lipid content and EPA level in the engineered strains. The effect of pex mutation on peroxisome morphology and function was studied to understand the underlying mechanism. The insertion sites in a high EPA strain was mapped out by genome walk and genome sequencing. This allowed us to fully characterize the strain and understand key factors contributing to fatty acid elongation, desaturation and lipid accumulation. In addition, we investigated Y. lipolytica Snf1 kinase signal transduction pathway for its role as a regulator of lipid metabolism. These results suggested that there are multiple factors influencing levels of EPA and lipid production in Y. lipolytica.