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

Brewing lager yeast (Saccharomyces pastorianus) is exposed to stressful conditions during beer fermentation, including ethanol toxicity. In response to ethanol toxicity, various biological mechanisms are modulated, including lipid biosynthesis. It is well known that during beer fermentation, the composition of yeast membranes changes 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 hubs for inter-organellar communication and modulating the activity of mechanisms necessary for ethanol tolerance, such as proteostasis and autophagy. Unfortunately, little is known about the interplay between autophagy, lipid metabolism, and proteostasis (ALP) in lager cells during beer fermentation. Therefore, transcriptome analyses using publicly available DNA microarray data obtained from lager yeast cells were used to identify all the ALP-associated genes that were upregulated during beer fermentation compared to yeast biomass propagation. Thereafter, a top-down systems biology analysis was applied, involving constructing an ALP-associated shortest-pathway protein-protein interaction network (ALP network), identifying important nodes and communities within the ALP network, and identifying the overrepresented biological processes and cellular components using a Gene Ontology (GO) analysis. The transcriptome analyses indicated the upregulation of 204 non-redundant ALP-associated genes during beer fermentation, whose respective proteins interact in the shortest-pathway ALP network. Thirteen communities were selected from the ALP network, and they were associated with multiple overrepresented GO biological processes and cellular components, such as mitophagy, cytoplasm-to-vacuole transport, piecemeal microautophagy of the nucleus, endoplasmic reticulum (ER) stress, ergosterol and lipid biosynthesis, LDs, ER membrane, and phagophore assembly. These results indicate that ethanol tolerance in lager yeasts could be due to the modulation of proteostasis and various forms of autophagy by lipid biosynthesis and LDs, thus highlighting the importance of lipids for beer fermentation.