RT Journal Article T1 Metabolic-inhibitor profiling links phenotype and transcriptome of Lachancea thermotolerans to wine fermentation chemistry A1 Jimena López, Samuel A1 Vicente Sánchez, Javier A1 Benito Sáez, Santiago A1 Marquina Díaz, Domingo A1 Santos de la Sen, Antonio AB 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. PB Elsevier YR 2025 FD 2025-09 LK https://hdl.handle.net/20.500.14352/124626 UL https://hdl.handle.net/20.500.14352/124626 LA eng NO Jimena-López S, Vicente J, Benito S, Marquina D, Santos A. Metabolic-inhibitor profiling links phenotype and transcriptome of Lachancea thermotolerans to wine fermentation chemistry. Food Chemistry: Molecular Sciences 2025;11:100301. https://doi.org/10.1016/j.fochms.2025.100301. NO AcknowledgementsFunding for this research was provided by the LowpHWine Companies Consortia through the CDTI project LowpHWine (IDI-20210391) and the Spanish Ministry of Science and Innovation under the VinSegCalClim project (PID2020-119008RB-I00). Javier Vicente conducted this research under a fellowship from Complutense University of Madrid (CT58/21-CT59/21). Samuel Jimena conducted this research under an INVESTIGO (CT19/23-INVM-18) contract from the Spanish Ministry of Labour and Social Economy. NO Ministerio de Ciencia e Innovación (España) NO Ministerio de Trabajo y Economía Social (España) NO Universidad Complutense de Madrid NO Consorcio LowpHWine DS Docta Complutense RD 8 jun 2026