PNNL

Abstract

The yeast Yarrowia lipolytica is a potent accumulator of lipids and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis Y. lipolytica and identified how two opposite regulatory states both result in lipid accumulation. The study involved the comparison of a strain overexpressing diacylglycerol acyltransferase (DGA1) with a control strain grown under either nitrogen or carbon limited conditions. A strong correlation was observed between the responses on the levels of transcript and protein. Combination of DGA1 overexpression with nitrogen limitation resulted in high-level of lipid accumulation accompanied by down regulation of various amino acid biosynthetic pathways, with leucine in particular, and these changes were further correlated with a decrease in metabolic fluxes. This downregulation was supported by a measured decrease in the level of 2-isopropylmalate, an intermediate of leucine biosynthesis. Combining the multi omics data with putative transcription factor binding motifs uncovered a contradictory role for TORC1 in controlling lipid accumulation, likely mediated through 2-isopropylmalate and a Leu3-like transcription factor.