Self-produced hydrogen sulfide improves ethanol fermentation by Saccharomyces cerevisiae and other yeast species

Hydrogen sulfide (H 2 S) is a gas produced endogenously in organisms from the three domains of life. In mammals, it is involved in diverse physiological processes, including the regulation of blood pressure, and its effects on memory. In contrast, in unicellular organisms the physiological role of H 2 S has not been studied in detail. In yeast, for example, in the winemaking industry H 2 S is an undesirable byproduct because of its rotten egg smell; however, its biological relevance during fermentation is not well understood. The effect of H 2 S in cells is linked to a posttranslational modification in cysteine residues known as S-persulfidation. We evaluated S-persulfidation in the Saccharomyces cerevisiae proteome. We screened S-persulfidated proteins from cells growing in fermentable carbon sources and we identified several glycolytic enzymes as S-persulfidation targets. Pyruvate kinase, catalyzing the last irreversible step of glycolysis, increased its activity in the presence of a H 2 S donor. Yeast cells treated with H 2 S increased ethanol production; moreover, mutant cells that endogenously accumulated H 2 S produced more ethanol and ATP during the exponential growth phase. This mechanism of the regulation of the metabolism seems to be evolutionarily conserved in other yeast species, because H 2 S induces ethanol production in the pre-Whole Genome Duplication species Kluyveromyces marxianus and Meyerozyma guilliermondii . Our results suggest a new role of H 2 S in the regulation of the metabolism during fermentation.