%0 Journal Article %A Jimena López, Samuel %A Vicente Sánchez, Javier %A Benito Sáez, Santiago %A Marquina Díaz, Domingo %A Santos de la Sen, Antonio %T Metabolic-inhibitor profiling links phenotype and transcriptome of Lachancea thermotolerans to wine fermentation chemistry %D 2025 %U https://hdl.handle.net/20.500.14352/124626 %X We applied targeted metabolic inhibitors to 145 Lachancea thermotolerans strains to uncover fermentation traits with direct relevance to wine quality. Oxamate, a lactate dehydrogenase inhibitor, reduced lactic acid and totaltitratable acidity by 21% and 26%, respectively, while increasing succinic acid and pH without affecting ethanol levels, offering a promising strategy to fine-tune wine freshness and balance. Notably, industrial grape-associatedstrains (clusters C4–C6) maintained robust growth under oxamate stress, unlike wild strains, positioning oxamate resistance as a practical marker for selecting high-performing, acidifying yeasts for winemaking. Additionalinhibitors such as metformin shifted redox metabolism, significantly enhancing glycerol (+25%) and acetic acid (+319%) production. Transcriptomic analyses showed that OXA alone, and even more so the DSF + OXAcombination, repressed LDH2 and upregulated GPD1 and oxidative phosphorylation genes, whereas MET caused only moderate changes. This integrated phenomic-transcriptomic approach not only provides valuable tools foryeast screening but also defines a roadmap for optimizing wine composition through the precision selection of L. thermotolerans strains. %~