Identification of longevity strains of Saccharomyces cerevisiae under high-glucose conditions

<title>Abstract</title> <p> Excessive glucose concentrations accelerate cellular aging and impair fermentation robustness in industrial <italic>Saccharomyces cerevisiae</italic> , yet how yeast adapts to persistent glucose excess while maintaining long-term viability is not fully understood. In this study, adaptive laboratory evolution (ALE) was carried out under 300 g L ^− 1 glucose and combined with ethyl methanesulfonate (EMS) mutagenesis to generate multiple independent longevity-adapted lineages of the laboratory haploid strain BY4742. Chronological lifespan, growth kinetics, transcriptomics, and non-targeted metabolomics were integrated to characterize the underlying adaptive changes. The evolved strains showed significantly greater cumulative survival across the chronological lifespan assay, together with improved survival under high-glucose stress and shortened lag phases without major reductions in growth rate. Transcriptomic analysis revealed a conserved ribosome-associated adaptive core shared among lineages. Beyond this common foundation, W2 strains primarily remodeled translational allocation and biosynthetic pathways, E strains emphasized proteostasis(definition), autophagy(definition), membrane remodeling, and mitochondrial functions, and W3 strains showed extensive restructuring of central carbon metabolism, protein folding, and quality control. Despite this transcriptomic divergence, metabolomic remodeling showed clear convergence. Tryptophan metabolism was the most consistent shared signature, accompanied by coordinated alterations in kynurenine, xanthurenic acid, nicotinamide, and indole-3-acetic acid. These findings are consistent with a hierarchical model in which distinct transcriptional trajectories converge on remodeling of tryptophan-kynurenine metabolism and NAD ⁺ -associated nucleotide and redox networks, offering a systems-level framework for understanding adaptive aging and a basis for engineering robust industrial yeast strains. </p>