U Texas at Austin researchers rewire yeast for high lipid generation; 60x improvement over parent strains
Researchers at the University of Texas at Austin’s Cockrell School of Engineering have rewired the native metabolism of the yeast Yarrowia lipolytica for superior production of lipids (lipogenesis). Tri-level metabolic control resulted in saturated cells containing upwards of 90% lipid content and titres exceeding 25 g l−1 lipids—a 60-fold improvement over parental strain and conditions.
In the study, reported in the journal Nature Communications, the researchers genetically modified Y. lipolytica by both removing and overexpressing specific genes that influence lipid production. In addition, the team identified optimum culturing conditions that differ from standard conditions.
Through this rewiring effort, we advance fundamental understanding of lipogenesis, demonstrate non-canonical environmental and intracellular stimuli and uncouple lipogenesis from nitrogen starvation. The high titres and carbon-source independent nature of this lipogenesis in Y. lipolytica highlight the potential of this organism as a platform for efficient oleochemical production.—Blazeck et al.
Traditional methods to increase lipids yield rely on nitrogen starvation to trick yeast cells into storing fat and materials. The new study, led by assistant professor Dr. Hal Alper, provides a mechanism for growing lipids without nitrogen starvation. The research has resulted in a technology for which UT Austin has applied for a patent.
Our cells do not require that starvation. That makes it extremely attractive from an industry production standpoint.—Hal Alper
At 90% lipid levels, the platform produces the highest levels of lipid content created so far using a genetically engineered yeast cell. To compare, other yeast-based platforms yield lipid content in the 50-80% range. However, these alternative platforms do not always produce lipids directly from sugar as the UT Austin technology does.
The team subsequently converted the lipids to biodiesel. The advantages of using the yeast cells to produce commercial-grade biodiesel are that yeast cells can be grown anywhere, do not compete with land resources and are easier to alter genetically than other sources of biofuel.
By genetically rewiring Yarrowia lipolytica, Dr. Alper and his research group have created a near-commercial biocatalyst that produces high levels of bio-oils during carbohydrate fermentation. This is a remarkable demonstration of the power of metabolic engineering.—Dr. Lonnie O. Ingram, director of the Florida Center for Renewable Chemicals and Fuels at the University of Florida
Alper and his team are continuing to find ways to further enhance the lipid production levels and develop new products using this engineered yeast.
This research was funded by the Office of Naval Research Young Investigator Program, the DuPont Young Professor Grant and the Welch Foundation under grant F-1753.
John Blazeck, Andrew Hill, Leqian Liu, Rebecca Knight, Jarrett Miller, Anny Pan, Peter Otoupal & Hal S. Alper (2014) “Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production,” Nature Communications 5, Article number: 3131 doi: 10.1038/ncomms4131