Recent Advances in Cofactor Engineering Applied to Modulate Esters or Higher Alcohols in Fermented Beverages of Saccharomyces cerevisiae

Cofactors are small molecules or ions that participate in enzymatic reactions as essential carriers of electrons, atoms, or functional groups, thereby governing cellular redox balance and energy metabolism. In the yeast Saccharomyces cerevisiae, the availability of cofactors such as NAD(H), NADP(H), CoA, and acetyl-CoA directly influences the flux through biosynthetic pathways leading to aroma-active compounds. Esters and higher alcohols are the two most important families of volatile flavor compounds in fermented alcoholic beverages. Their synthesis is intimately linked to the intracellular levels and ratios of these cofactors. This review summarizes recent progress in cofactor engineering strategies aimed at modulating the production of esters, higher alcohols, and 2,3-butanediol in S. cerevisiae. We discuss the underlying metabolic pathways, highlight key studies that manipulate cofactor pools to redirect carbon flux, and examine emerging tools (e.g., riboswitches, fine-tuned promoter systems) that enable precise cofactor balancing. Finally, we outline future challenges and opportunities for applying cofactor engineering to design yeast cell factories with tailored flavor profiles.