Baker’s Yeast Saccharomyces cerevisiae: Going way Beyond Baking!

The production of metabolites through metabolically engineered microorganisms has been a global practice since the advent of recombinant DNA technology in the 1970s, successfully leading to the production of human growth hormone in Escherichia coli. The baker’s yeast Saccharomyces cerevisiae, in addition to its immense importance as a fermentative microorganism in the food industry, has been recognized as an eukaryotic model system for metabolic engineering and heterologous production of metabolites, owing to its highly explored metabolic knowledge bank, high transformation efficiency, as well as the availability of the complete genomic information. Furthermore, these properties have facilitated rigorous genetic manipulation of this microorganism. Moreover, the emergence of novel genome engineering approaches like ZFN, TALEN, and CRISPR-Cas has accelerated the process of metabolic engineering of this gold-standard organism in order to suit the specific industrial, pharmaceutical, and nutraceutical needs. In this article, we have attempted to provide an overview of the metabolic engineering strategies and concepts for the production of important classes of compounds like vitamins, phytocompounds, drugs, and biofuels by genetically engineered S. cerevisiae. We have summarized key metabolites for which production titers have been significantly enhanced in genetically engineered yeast systems; for example, the yield of Vitamin A reached 3432 mg/L in optimized strains, while 7-dehydrocholesterol (7-DHC), a precursor of Vitamin D, was produced at 1328 mg/mL through genome integration. Additionally, considerable improvements were achieved for important phytocompounds such as resveratrol, with titres up to 4.1 g/L. Notably, advanced biofuels, including ethanol and isobutanol, have achieved titres of 114.71 g/L and 364 mg/L, respectively, demonstrating the metabolic versatility of S. cerevisiae. Furthermore, in this article, we have highlighted the challenges and future opportunities for the metabolic bioengineering of S. cerevisiae.