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(629g) Engineering Redox Homeostasis and Aldehyde Detoxification to Improve Lipid Production in Y. Lipolytica

Xu, P., MIT
Qiao, K., Massachusetts Institute of Technology
Stephanopoulos, G. N., Massachusetts Institute of Technology

Yarrowia lipolytica, an oleaginous yeast, can naturally accumulate large quantity of neutral lipids using a variety of carbon sources. Previous metabolic engineering efforts working on the acyl-CoA related pathways (Tai M et al, Metabolic engineering, 2013) have resulted in efficient triacylglyceride producers by increasing the carbon flux towards malonyl-CoA and sequestrating fatty acyl-CoAs in neutral lipids. One major obstacle for efficient production of lipids in Y. lipolytica is pertinent to the unique nitrogen starvation conditions which predispose the cell in an unfavorable physiological states and lead to relatively low productivity and yield. We have recently identified an oxidative stress defense mechanism to regulate lipid biosynthesis in Y. lipolytica. By scavenging reactive oxygen and aldehyde species, we were able to optimize the cell physiology and morphology and achieved very high level of oil content and lipid productivity in our previously engineered Y. lipolytica lipid overproducers. The strategies reported in this study represent a promising solution to develop a yeast biorefinery platform that potentially upgrades low value carbons to high value commodity chemicals.