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Adaptive evolution of industrial Saccharomyces cerevisiae strains for improved glycerol utilization and optimization of key process parameters in bioreactors
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DOI：10.1016/j.procbio.2026.03.008.png)
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Abstract
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Glycerol is an attractive carbon and energy source for many microorganisms, and it is a valuable, low-cost substrate for industrial fermentations. However, one of the most widely used industrial microorganisms, Saccharomyces cerevisiae, is generally unable to efficiently utilize glycerol owing to physiological and metabolic constraints. In this study adaptive evolution (AE) was applied to non-engineered, industrial S. cerevisiae strains, with a particular focus on pH as a selective pressure in bioreactor-scale fermentations. After 152 generations, S. cerevisiae Strain3 demonstrated notable glycerol consumption, in contrast to the wild-type strain, which showed no glycerol consumption, along with an enhanced maximum specific growth rate from 0.05 h- 1 to 0.24 h- 1 at 20 g L- 1 glycerol concentration. Further experiments with Strain3 at pH 4.0 under pH-controlled conditions and with two different initial cell concentrations demonstrated complete glycerol consumption within 30 h in all fermentations when the pH was maintained constant at 4.0. Higher initial cell concentrations led to more rapid glycerol consumption, highlighting its significant role in fermentation performance. This study provides the first comparative genomic analysis of glycerol-adapted and wild-type S. cerevisiae, revealing 1254 unique variants in the adapted strain. Enrichment of mutations in regulatory regions suggests transcriptional reprogramming, whereas mutations in FPS1 indicate improved glycerol uptake and metabolism. Genome-wide variation patterns highlight genome plasticity as a key adaptive mechanism for growth on glycerol.
Keywords:
Industrial yeast strains
Adaptive evolution
Glycerol utilization
PH-controlled
Batch operational mode
Genomic difference
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