Engineering Lipid Homeostasis Mechanisms for an Efficient Production of Fatty Acid-Derived Chemicals in S. Cerevisiae

Saccharomyces cerevisiae has been widely studied and applied as a platform for production of fatty-acid derived chemicals. Although engineering of these cells is today a somewhat straightforward process, overcoming the natural limitations of this organism for accumulation and production of lipid molecules in high amounts brings forward many barriers that deny the progress of metabolic engineering as a tool for industry. A root factor that negatively reacts towards engineering attempts is the tight and sometimes not well understood regulation mechanisms surrounding lipid metabolism. Furthermore, recent progress in cell and molecular biology have been revealing either new concepts of lipid pool regulation and associations between lipid metabolism and many other cell homeostasis processes.

In this study, we explore strategies that target factors related to lipid metabolism regulation which could turn out as key points to unlock control and fine-tuning of fatty acid and acyl-CoA-related pathways for production of fatty acid-derived molecules, such as fatty alcohols, in an efficient way. Due to the unknown characteristics of such processes, we use a combination of rational and blind engineering approaches to both achieve desirable phenotypes and understand the process underlying it after analysis.