Spontaneous Attenuation of Alcoholic Fermentation via the Dysfunction of Cyc8p in Saccharomyces cerevisiae

A cell population characterized by the release of glucose repression and known as [GAR] emerges spontaneously in the yeast Saccharomyces cerevisiae. This study revealed that the [GAR] variants exhibit retarded alcoholic fermentation when glucose is the sole carbon source. To identify the key to the altered glucose response, the gene expression profile of [GAR] cells was examined. Based on RNA-seq data, the [GAR] status was linked to impaired function of the Cyc8p-Tup1p complex. Loss of Cyc8p led to a decrease in the initial rate of alcoholic fermentation under glucose-rich conditions via the inactivation of pyruvate decarboxylase, an enzyme unique to alcoholic fermentation. These results suggest that Cyc8p can become inactive to attenuate alcoholic fermentation. These findings may contribute to the elucidation of the mechanism of non-genetic heterogeneity in yeast alcoholic fermentation.