Metabolic impact of redox cofactor perturbations on the formation of aroma compounds in Saccharomyces cerevisiae.

Redox homeostasis is a fundamental requirement to the sustainment of metabolism, energy generation and growth in Saccharomyces cerevisiae. Redox cofactors NADH and NADPH are among the most highly connected metabolites in metabolic networks. Changes in their concentrations may induce widespread changes in metabolism. Redox imbalances were achieved here thanks to a dedicated biological tool overexpressing native NADH- or engineered NADPH-dependent 2,3-butanediol dehydrogenase in presence of acetoin. We report that the targeted perturbation of the cofactors balances (NAD(+)/NADH or, in a lesser extent, NADP(+)/NADPH) significantly affects the production of volatile compounds. In most cases, variations of the redox state of yeasts modified the formation of all compounds from the same biochemical pathway (isobutanol, isoamyl alcohol and their derivatives) or chemical class (ethyl esters), irrespective of the cofactors. These coordinated responses were found to be closely linked to the impact of redox on the availability of intermediates of the central carbon metabolism. This is the case for α-keto acids and acetyl-CoA, which are precursors for the synthesis of many volatile compounds. We also demonstrated that changes in the availability of NADH selectively affect the synthesis of some volatile molecules, as methionol, phenylethanol, and propanoic acid, reflecting the specific cofactor requirements of the dehydrogenases involved in their formation. Our findings point out that both the availability of precursors from the central carbon metabolism and the accessibility to reduced cofactors contribute to the modulation of the formation of volatile compounds by the cell redox status.