Fig. 1

Metabolomics-based strategy of phenotype improvement. Various mutant strains of S. cerevisiae are cultivated in the presence of 1-butanol stress to measure their tolerances. These strains are also cultivated under the non-stress condition for metabolome analysis. The metabolomics and tolerance data are combined to construct a regression model, which provides information on which metabolites are strongly associated with tolerance. On the assumption that these metabolites have a causal relationship with tolerance, the corresponding metabolic pathways are examined, and gene deletion targets predicted to modify metabolite pools in the direction associated with increased tolerance are then identified. Finally, new deletion strains are obtained, and their tolerances and metabolite pools are measured to validate the model predictions