Dynamic genome-scale modeling of Saccharomyces cerevisiae unravels mechanisms for higher alcohol and ester formation during alcoholic fermentation

Fermentation employing Saccharomyces cerevisiae has produced alcoholic beverages and bread for millennia. More recently, S. cerevisiae has been used to manufacture specific metabolites for the food, pharmaceutical, and cosmetic industries. Among the most important of these metabolites are compounds associated with desirable aromas and flavors, including higher alcohols and esters. While the physiology of yeast has been well-studied, its metabolic modulation leading to aroma production under industrial relevant scenarios such as winemaking is still unclear. Furthermore, what are the underlying metabolic mechanisms explaining the conserved and varying behavior of yeasts regarding aroma formation under enological conditions? Dynamic flux balance analysis (dFBA) was employed to answer these questions using the latest genome-scale metabolic model (GEM) of S. cerevisiae. Although we found several conserved mechanisms among wine yeasts, e.g., acetate ester formation is dependent on intracellular metabolic acetyl-CoA/CoA levels, and the formation of ethyl esters facilitates the removal of toxic fatty acid from cells using CoA, species-specific mechanisms were also found, e.g., carbohydrate accumulation induces redox restrictions later for strain Uvaferm. In conclusion, our new metabolic model of yeast under enological conditions revealed key metabolic mechanisms in wine yeasts, which will aid future research strategies to optimize their behavior in industrial settings.