pH selectively regulates citric acid and lipid production in Yarrowia lipolytica W29 during nitrogen-limited growth on glucose

Yarrowia lipolytica has been used to produce both citric acid and lipid-based bioproducts at high titers. In this study, we found that pH differentially affects citric acid and lipid production in Y. lipolytica W29, with citric acid production enhanced at more neutral pH's and lipid production enhanced at more acid pH's. To determine the mechanism governing this pH-dependent switch between citric acid and lipid production, we profiled gene expression at different pH's and found that the relative expression of multiple transporters is increased at neutral pH. These results suggest that this pH-dependent switch is mediated at the level of citric acid transport rather than changes in the expression of the enzymes involved in citric acid and lipid metabolism. In further support of this mechanism, thermodynamic calculations suggest that citric acid secretion is more energetically favorable at neutral pH's, assuming the fully protonated acid is the substrate for secretion. Collectively, these results provide new insights regarding citric acid and lipid production in Y. lipolytica and may offer new strategies for metabolic engineering and process design.