Lysine analogue-driven adaptive evolution produces lysine-overproducing wine yeast strains
Journal article, 2026
Lysine, though a poor nitrogen source for Saccharomyces cerevisiae, is rapidly consumed during wine fermentation and has been linked to enhanced oxidative and sulfur dioxide resistance. To investigate and harness this phenotype, the industrial wine strain P14 was subjected to adaptive laboratory evolution under increasing concentrations of the toxic lysine analogue S-aminoethyl cysteine (AEC). The resulting evolved isolates accumulated up to tenfold more intracellular lysine, displayed elevated reduced glutathione, and exhibited substantially decreased ROS levels while maintaining robust fermentation performance. Whole-genome sequencing revealed extensive genomic rearrangements and recurrent mutations associated with lysine biosynthesis. Among these, the LYS21V127F mutation emerged as the major driver of lysine overproduction and AEC resistance. CRISPR/Cas9 reconstruction of this allele in multiple wine yeasts confirmed its causal role and conferred a competitive advantage during fermentation. These findings demonstrate the effectiveness of AEC-driven evolution for generating lysine-overproducing wine yeasts and highlight LYS21 feedback-resistance as a key metabolic innovation.
Adaptive laboratory evolution (ALE)
Wine fermentation
Glutathione metabolism
Genome evolution
Lysine overproduction
Homocitrate synthase (LYS21)
Author
Sara Muñiz Calvo
Chalmers, Life Sciences, Systems and Synthetic Biology
Spanish National Research Council (CSIC)
Elena Valera-García
Spanish National Research Council (CSIC)
Judit Pardo
Spanish National Research Council (CSIC)
María Vázquez
Spanish National Research Council (CSIC)
Andrés Planells-Cárcel
Spanish National Research Council (CSIC)
Javier Alonso-del-Real
Spanish National Research Council (CSIC)
Ying Su
Northwest A&F university
José María Heras
Lallemand Sas
Anne Ortiz-Julien
Lallemand Sas
Estéfani García-Ríos
University of La Rioja
José Manuel Guillamón
Spanish National Research Council (CSIC)
Food Research International
0963-9969 (ISSN) 18737145 (eISSN)
Vol. 245 120791Subject Categories (SSIF 2025)
Evolutionary Biology
Food Biotechnology
Genetics and Genomics
DOI
10.1016/j.foodres.2026.120791
Related datasets
Dataset [dataset]
URI: http://hdl.handle.net/10261/403811