Metabolic engineering in the host Yarrowia lipolytica

Abstract

The nonconventional, oleaginous yeast, Yarrowia lipolytica is rapidly emerging as a valuable host for the production of a variety of both lipid and nonlipid chemical products. While the unique genetics of this organism pose some challenges, many new metabolic engineering tools have emerged to facilitate improved genetic manipulation in this host. This review establishes a case for Y. lipolytica as a premier metabolic engineering host based on innate metabolic capacity, emerging synthetic tools, and engineering examples. The metabolism underlying the lipid accumulation phenotype of this yeast as well as high flux through acyl-CoA precursors and the TCA cycle provide a favorable metabolic environment for expression of relevant heterologous pathways. These properties allow Y. lipolytica to be successfully engineered for the production of both native and nonnative lipid, organic acid, sugar and acetyl-CoA derived products. Finally, this host has unique metabolic pathways enabling growth on a wide range of carbon sources, including waste products. The expansion of carbon sources, together with the improvement of tools as highlighted here, have allowed this nonconventional organism to act as a cellular factory for valuable chemicals and fuels.

Keywords: Biofuel; Metabolic engineering; Oleochemicals; Synthetic biology; Yarrowia lipolytica.