Rethinking the role of lipids in lager yeast cell during beer fermentation from a transcriptome and systems biology perspective

Brewing lager yeasts () should deal with stressful conditions during beer fermentation, including ethanol toxicity. In response to ethanol toxicity, different biological mechanisms are modulated, including lipid biosynthesis. It is well known that during beer fermentation, the composition of yeast membranes change in response to ethanol toxicity, making it less fluid and permeable. Additionally, neutral lipids and lipid droplets (LDs) are produced in response to ethanol toxicity. LDs are membranous organelles that transport lipids and proteins, acting as a hub for inter-organellar communication and module the activity of mechanisms necessary for ethanol tolerance, like proteostasis and autophagy. Unfortunately, little is known about the interplay of lipid biosynthesis, proteostasis, and autophagy in lager cells during beer fermentation. Thus, a transcriptome single and meta-analysis using publically available DNA microarray data of lager yeast cells in conditions of beer fermentation and cell biomass propagation was used to select all the upregulated genes associated to autophagy, lipid biosynthesis, and proteostasis (ALP) during beer fermentation. Following transcriptome data collection, a top-down systems biology analyses was applied with the design of an ALP-associated shortest pathway protein-protein network (ALP network), selection of central nodes and communities within ALP network, and the observation of the overrepresented biological processes and cellular components by gene ontology (GO) analysis. The transcriptome results show the upregulation of 204 non redundant ALP genes in conditions of beer fermentation, whose respective proteins interact in a shortest pathway ALP network. Thirteen communities where selected from ALP network containing overrepresented processes and components like mitophagy, cytoplasm-to-vacuole transport, pieacemeal micrautophagy of the nucleus, endoplasmic reticulum (ER) stress, ergosterol and lipid biosynthesis, LDs, ER membrane, phagophore assembly, among others. These results indicated that ethanol tolerance in lager yeasts could be due to the modulation of proteostasis and different forms of autophagy by lipid biosynthesis and LDs, and thus extending the importance of lipids for beer fermentation.