Engineering of a High Lipid Producing Yarrowia Lipolytica Strain

Microbial lipid production has received interest both for the synthesis of specialty lipids and for the production of fuels and chemicals from various feedstocks. Microbial lipids are produced by many oleaginous organisms including the well characterized yeast Yarrowia lipolytica. Lipid yield in oleaginous organisms can be increased through the up-regulation and/or down-regulation or deletion of genes involved in the lipid pathway. In this study, we describe a strain-engineering strategy applying combinatorial screening of overexpression and deletion genetic targets that led to the construction of a high lipid-producing yeast biocatalyst. The resulting strain NS432 that combines three genetic modifications selected for their effect on lipid production reached 76% fatty acid content and 0.21 g lipid per g glucose yield in batch glucose fermentation. In fed-batch glucose fermentation NS432 produced 92 g/L lipid at a productivity of 0.68 g.L-1.hr^-1, which is 3.7 and 3.2-fold higher in titer and productivity, respectively, over previously reported Y. lipolytica engineered biocatalysts.