Nutrient Signaling via the TORC1-Greatwall-PP2A Pathway Is Responsible for the High Initial Rates of Alcoholic Fermentation in Sake Yeast Strains of Saccharomyces cerevisiae.

sake yeast strain Kyokai no. 7 (K7) and its relatives carry a homozygous loss-of-function mutation in the gene, which encodes a Greatwall family protein kinase. Disruption of in nonsake yeast strains leads to improved alcoholic fermentation, indicating that the defect in Rim15p is associated with the enhanced fermentation performance of sake yeast cells. In order to understand how Rim15p mediates fermentation control, we here focused on target-of-rapamycin protein kinase complex 1 (TORC1) and protein phosphatase 2A with the B55δ regulatory subunit (PP2A), complexes that are known to act upstream and downstream of Rim15p, respectively. Several lines of evidence, including our previous transcriptomic analysis data, suggested enhanced TORC1 signaling in sake yeast cells during sake fermentation. Fermentation tests of the TORC1-related mutants using a laboratory strain revealed that TORC1 signaling positively regulates the initial fermentation rate in a Rim15p-dependent manner. Deletion of the gene, encoding B55δ, abolished the high fermentation performance of Rim15p-deficient laboratory yeast and sake yeast cells, indicating that PP2A mediates the fermentation control by TORC1 and Rim15p. The TORC1-Greatwall-PP2A pathway similarly affected the fermentation rate in the fission yeast , strongly suggesting that the evolutionarily conserved pathway governs alcoholic fermentation in yeasts. It is likely that elevated PP2A activity accounts for the high fermentation performance of sake yeast cells. Heterozygous loss-of-function mutations in found in K7-related sake strains may indicate that the Rim15p-deficient phenotypes are disadvantageous to cell survival. The biochemical processes and enzymes responsible for glycolysis and alcoholic fermentation by the yeast have long been the subject of scientific research. Nevertheless, the factors determining fermentation performance are not fully understood. As a result, the industrial breeding of yeast strains has required empirical characterization of fermentation by screening numerous mutants through laborious fermentation tests. To establish a rational and efficient breeding strategy, key regulators of alcoholic fermentation need to be identified. In the present study, we focused on how sake yeast strains of have acquired high alcoholic fermentation performance. Our findings provide a rational molecular basis to design yeast strains with optimal fermentation performance for production of alcoholic beverages and bioethanol. In addition, as the evolutionarily conserved TORC1-Greatwall-PP2A pathway plays a major role in the glycolytic control, our work may contribute to research on carbohydrate metabolism in higher eukaryotes.