U.S. Department of Energy

Pacific Northwest National Laboratory

Lipid Metabolism Mystery Could be Key to Future ‘Microbial Cell Factory’

Regulation of Y. lipolytica metabolism. (A) Transcriptional downregulation of leucine biosynthesis. The boxes indicate z scores, incorporating both fold change and significance values. Regulation scores indicate correlations between all three levels and are calculated as detailed in Materials and Methods.

The Science                      

The yeast Yarrowia lipolyticais considered a promising “microbial cell factory” for producing biofuels and oleochemicals, but researchers need to understand how the yeast’s lipid metabolism is regulated so that they can manipulate it. In this study, researchers focused on the lipogenesis—or metabolic formation of fat—of Y. lipolyticaby analyzing one of its genes, diacylglycerol acyltransferase (DGA1), under two opposite conditions. From this experiment, researchers observed how environmental factors impact lipid accumulation. 

The Impact

Lipid metabolism is involved in many diseases but it is also vital to the development of the microbial cell factories that may someday provide us with sustainable fuels and oleochemicals. This research introduces foundational work to further unravel the regulation of lipid accumulation in eukaryal cells so that they can be manipulated for other uses.


Various factors can influence lipid metabolism, including the environment and genetics. Lipid accumulation in Y. lipolyticais a complex trait where both genetic and environmental factors have influence. For the purposes of this study, researchers used nutrient limitation (environmental) and DGA1 overexpression (genetic) as factors. 

Researchers observed clear phenotypical (or trait) changes on the level of lipid accumulation, induced by both genetic and environmental factors, and they linked the phenotypic changes to regulatory ones. The environmental factor—in this case limited nitrogen—increased lipid accumulation in all conditions where it was also introduced with the genetic factor (overexpression of DGA1). And the pathway most strongly affected by this pairing of factors was leucine biosynthesis, which is also implicated in other complex phenotypes. These findings show that leucine funtions as a key metabolic node in diverse phenotypes across yeast species.


This work was funded by the Genome Science Program, Office of Biological and Environmental Research; the GSP-funded Pan-omics Program at PNNL; and the Novo Nordisk Foundation and the Knut and Alice Wallenberg Foundation. 


Kerkhoven EJ, et al. 2017. “Leucine biosynthesis is involved in regulating high lipid accumulation in Yarrowia lipolytica.” mBio8:e00857-17. doi.org/10.1128/ mBio.00857-17


June 2017
| Pacific Northwest National Laboratory