Cysteine, methionine and pantothenic acid remodel the Saccharomyces cerevisiae transcriptome and volatile sulphur compound metabolome during alcoholic fermentation

Yeast nitrogen and vitamin nutrition are fundamental levers for managing wine quality, yet the specific mechanisms linking nutrient availability to sulfur aroma formation remain poorly understood. This study explored the impact of methionine, cysteine, and pantothenic acid (vitamin B5)-nutrients with direct, pivotal roles in sulfur metabolic pathways-on the S. cerevisiae transcriptome and VSC metabolome during fermentation. Our findings reveal that methionine and cysteine catabolic routes act as isolated compartments; the genes responsible for bridging these two pathways remain transcriptionally silent in the presence of high cysteine or methionine availability. This lack of metabolic crossover leads to highly specific VSC signatures. Methionine exerts only a limited influence on global gene expression and primarily drives the production of methylthio-compounds via the Ehrlich pathway. Cysteine triggers a starvation-like transcriptomic response and promotes a diverse range of thiols and thioesters. Pantothenic acid deficiency compromised yeast growth and fermentation efficiency, triggered extensive transcriptional changes in sulfur assimilation pathways, effectively redirecting flux toward non-Ehrlich catabolic products. Overall, this study provides a robust mechanistic basis for how sulphur amino acid and pantothenic acid levels can be targeted to modulate wine aroma profiles and prevent the development of reductive off-flavors.