Holistic Approaches in Lipid Production by Yarrowia lipolytica

Concerns about climate change have driven research on the production of lipid-derived biofuels as an alternative and renewable liquid fuel source. Using oleaginous yeasts for lipid synthesis creates the potential for cost-effective industrial-scale operations due to their ability to reach high lipid titer, yield, and productivity resulting from their unique metabolism. Yarrowia lipolytica is the model oleaginous yeast, with the best-studied lipid metabolism, the greatest number of genetic tools, and a fully sequenced genome. In this review we highlight multiomics studies that elucidate the mechanisms allowing this yeast to achieve lipid overaccumulation and then present several major metabolic engineering efforts that enhanced the production metrics in Y. lipolytica. Recent achievements that applied novel engineering strategies are emphasized. Yarrowia lipolytica is a model oleaginous yeast for the production of lipids and lipid-derived biofuels, studies of lipid metabolism, and the biosynthesis of various industrially important metabolites. Multiomics measurements and in silico metabolic modeling for Y. lipolytica deepens our understanding of the organism’s metabolism and aids in identifying the limiting steps in lipid biosynthesis. A variety of metabolic engineering attempts to enhance lipid production have been conducted, exploring the overexpression of fatty acid and triacylglyceride synthesis pathways and the deletion of antagonistic degradation pathways. More recent strategies involve a holistic understanding of limiting factors in lipid biosynthesis. These studies target the bottlenecks identified in previous omics studies and formulate metabolic engineering strategies accordingly.