Dynamic lipidomic insights into the adaptive responses of Saccharomyces cerevisiae to the repeated vacuum fermentation.

Vacuum fermentation is utilized in a wide range of life science industries and biomedical R&D. Little is known, however, on the effects of the vacuum on the yeast, and in particular, on the yeast lipidome that plays a central role in maintaining cell membrane and other vital (yeast) cell functions. The present study evaluated the adaptive responses of Saccharomyces cerevisiae to repeated vacuum fermentation by lipidomic analysis. We employed gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) and liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI/MS(n)) to quantify a total of 13 intermediate sterols and 139 phospholipid species of yeast cells. Principal components analysis found that the PI (phosphatidylinositol) 26:0, PI 28:0, PE (phosphatidylethanolamine) 32:1, and PE 34:1 were potential biomarkers to distinguish the vacuum fermentation process. Quantitative analysis showed that vacuum fermentation increased the synthesis of PI and the PC (phosphatidylcholine) species with short saturated acyl chains. The synthesis of PC via CDP-choline and turnover of PC were enhanced, instead of formation via methylation of PE. Additionally, increased PI at the expense of PE and PG (phosphatidylglycerol) was associated with enhancement of ethanol productivity. Vacuum fermentation caused eburicol accumulation, suggesting that vacuum can activate the branch of the ergosterol biosynthesis pathway. Eburicol decrease and PI increase contributed to recovery of cellular activities with oxygenating treatment. Ethanol productivity was increased by sixfold in vacuum-treated cells. These observations may allow the development of future mechanistic approaches to optimization of yeast fermentation under vacuum for bioindustry and life science applications. In particular, our findings on changes in lipid molecular species and the ergosterol biosynthesis pathway elucidate the defense responses of yeast cell membranes during the repeated vacuum fermentation, which by extension, provided an important lead insight on how best to protect the cell membranes from the extreme long-term stress conditions.