Genetic engineering of Saccharomyces cerevisiae for enhanced stress tolerance in industrial bioethanol production

Abstract:

Bioethanol is one of the most promising renewable alternatives to fossil fuels, with Saccharomyces cerevisiae serving as the principal industrial microorganism because of its high fermentation efficiency, genetic tractability, and long history of industrial application. However, industrial fermentation exposes yeast cells to multiple stresses, including ethanol toxicity, elevated temperature, osmotic stress, oxidative stress, and inhibitory compounds generated during lignocellulosic biomass pretreatment, all of which reduce cell viability and ethanol productivity. Recent advances in molecular biology, synthetic biology, and systems biology have significantly improved our understanding of the genetic and physiological mechanisms governing stress adaptation in S. cerevisiae. This review summarizes the major molecular mechanisms underlying stress tolerance, including stress signalling pathways, membrane homeostasis, antioxidant defence systems, and transcriptional regulation. It also discusses recent genetic engineering strategies such as metabolic engineering, CRISPR/Cas9- mediated genome editing, transcription factor engineering, adaptive laboratory evolution, and multi-omics-assisted strain development for constructing robust industrial yeast strains. Furthermore, the review highlights emerging approaches integrating systems biology and genome engineering to improve ethanol yield, fermentation stability, and industrial robustness under multiple environmental stresses. Future prospects focusing on multigene engineering, regulatory network optimization, and systems-level metabolic engineering are also discussed for developing next-generation yeast strains capable of sustaining efficient bioethanol production under industrial conditions.