RT Journal Article T1 Saccharomyces cerevisiae Cytosolic Thioredoxins Control Glycolysis, Lipid Metabolism, and Protein Biosynthesis under Wine-Making Conditions. A1 Picazo, Cecilia A1 McDonagh, Brian A1 Peinado, Jose A1 Barcena, Jose A A1 Matallana, Emilia A1 Aranda, Agustín K1 Saccharomyces cerevisiae K1 Fermentation K1 Glycolysis K1 Metabolomics K1 Oxidative stress K1 Proteomics K1 Thioredoxin-thioredoxin reductase systems K1 Wine K1 Yeasts AB Thioredoxins are small proteins that regulate the cellular redox state, prevent oxidative damage, and play an active role in cell repair. Oxidative stress has proven to be of much relevance in biotechnological processes when the metabolism of Saccharomyces cerevisiae is mainly respiratory. During wine yeast starter production, active dry yeast cytosolic thioredoxin Trx2p is a key player in protecting metabolic enzymes from being oxidized by carbonylation. Less is known about the role of redox control during grape juice fermentation. A mutant strain that lacked both cytosolic thioredoxins, Trx1p and Trx2p, was tested for grape juice fermentation. Its growth and sugar consumption were greatly impaired, which indicates the system's relevance under fermentative conditions. A proteomic analysis indicated that deletion of the genes TRX1 and TRX2 caused a reduction in the ribosomal proteins and factors involved in translation elongation in addition to enzymes for glycolysis and amino acid biosynthesis. A metabolomic analysis of the trx1Δ trx2Δ mutant showed an increase in most proteogenic amino acids, phospholipids, and sphingolipids and higher fatty acid desaturase Ole1p content. Low glycolytic activity was behind the reduced growth and fermentative capacity of the thioredoxin deletion strain. All three hexokinases were downregulated in the mutant strain, but total hexokinase activity remained, probably due to posttranslational regulation. Pyruvate kinase Cdc19p presented an early level of aggregation in the trx1Δ trx2Δ mutant, which may contribute to a diminished hexose metabolism and trigger regulatory mechanisms that could influence the level of glycolytic enzymes.IMPORTANCE Oxidative stress is a common hazardous condition that cells have to face in their lifetime. Oxidative damage may diminish cell vitality and viability by reducing metabolism and eventually leading to aging and ultimate death. Wine yeast Saccharomyces cerevisiae also faces oxidative attack during its biotechnological uses. One of the main yeast antioxidant systems involves two small proteins called thioredoxins. When these two proteins are removed, wine yeast shows diminished growth, protein synthesis, and sugar metabolism under wine-making conditions, and amino acid and lipid metabolism are also affected. Altogether, our results indicate that proper redox regulation is a key factor for metabolic adaptations during grape juice fermentation. PB American Society for Microbiology YR 2019 FD 2019-01-15 LK http://hdl.handle.net/10668/13464 UL http://hdl.handle.net/10668/13464 LA en NO Picazo C, McDonagh B, Peinado J, Bárcena JA, Matallana E, Aranda A. Saccharomyces cerevisiae Cytosolic Thioredoxins Control Glycolysis, Lipid Metabolism, and Protein Biosynthesis under Wine-Making Conditions. Appl Environ Microbiol. 2019 Mar 22;85(7):e02953-18 NO This work was funded by grants from the Spanish Ministry of Economy andCompetiveness MINECO (AGL2014-52984-R and AGL2017-83254-R to E.M. and A.A. andBFU2016-80006-P to J.A.B.). C.P. was supported by an F.P.I. fellowship from MINECO DS RISalud RD Apr 15, 2025