New Yeast Strains Optimized for Metabolic Engineering for Biobased Products with Reduced Ethanol Production

The yeast Saccharomyces cerevisiae is a favored industrial organism due to its robustness, low nutritional requirements, high tolerance to low pH, suitability for large-scale fermentation, and ease of genetic manipulation. However, this yeast preferentially converts fermentable sugars into ethanol over any other products of interest. Therefore, yeast strains engineered to produce other products are suboptimal due to their production of ethanol as a major byproduct that significantly diminishes the yield of the desired product. Strains have been developed to overcome this central challenge in yeast metabolic engineering by deleting either pyruvate decarboxylases, or alcohol dehydrogenases involved in ethanol formation, which dramatically reduces ethanol formation. However, if these enzymatic activities are completely eliminated, the resulting strains are unable to grow on glucose, a preferred industrial feedstock.  Restoration of growth of these strains on glucose can be achieved through directed evolution, but the resulting strains have impaired fitness and are difficult to work with. We have developed a new yeast strain that produces almost no ethanol, has improved fitness when growing on glucose, and overcomes many of the limitations that exist in currently available strains. This optimized strain can be engineered to produce different fuels or chemicals of interest from glucose, with significantly enhanced yields.