Zhiziong Xue, DuPont, Central Research Exptl. Station, Wilmington, DE 19880-0173
Clinical studies have shown that the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), commonly found in fish oil, confer wide ranging health benefits. However, concerns over the quality and sustainability of the fish oil supply have generated interest in alternative sources of these essential long-chain polyunsaturated fatty acids. We have developed a clean and sustainable fermentation source of EPA-enriched oil. Our approach has been to introduce the desaturase and elongase genes encoding an omega-3 fatty acid biosynthesis pathway into the oleaginous yeast, Yarrowia lipolytica. Coordinated expression of 19 copies of ten different heterologous genes enabled the synthesis of an oil that contained up to 40% EPA. We also extended the pathway by further introducing two more genes required for DHA biosynthesis, and demonstrated production of DHA. Versatile genetic tools that enable rational manipulation of the yeast genotype provided us a means to tailor its fatty acid composition for different applications. The unique feature and challenge for fatty acid production by fermentation, from host selection to process optimization, will be discussed.