A next-generation yeast chassis: comprehensive characterization of a robust fast-growing Saccharomyces cerevisiae

Robust and efficient hosts are necessary to facilitate advances in biotechnology. We unveil Saccharomyces cerevisiae strain XP as a promising new microbial chassis owing to its high growth rate and robustness. This strain has a doubling time of 48.2 min, which is 12.8 min faster than the model yeast S. cerevisiae S288C. Strain XP can grow well at low pH (≤ 3.0) and 30% (w/v) glucose under oligotrophic conditions. We establish a genetic manipulation toolbox using URA3 auxotroph and haploid strains, a Cre/loxP-based knocking-out method, and CRISPR/Cas9 genome editing tools. Genomic, transcriptomic and metabolomic data were analyzed in an integrated manner to characterize the strain. The multi-omics analysis reveals that changes in energy and essential nutrient metabolism are linked to rapid growth and robustness. A high-producing strain, XH352-D, was successfully constructed, which produced L-lactic acid with a titer of 52.6 g/L. Here, we comprehensively characterized a robust fast-growing yeast, laying foundation for its potential in industrial production of bulk chemicals.