Extending the G1 phase improves the production of lipophilic compounds in yeast by boosting enzyme expression and increasing cell size.

Cell phase engineering can significantly impact protein synthesis and cell size, potentially enhancing the production of lipophilic products. This study investigated the impact of G1 phase extension on resource allocation, metabolic functions, and the unfolded protein response (UPR) in yeast, along with the potential for enhancing the production of lipophilic compounds. In brief, the regulation of the G1 phase was achieved by deleting CLN3 (G1 cyclin) in various yeast strains. This modification resulted in a 83% increase in cell volume, a 76.9% increase in dry cell weight, a 82% increase in total protein content, a 41% increase in carotenoid production, and a 159% increase in fatty alcohol production. Transcriptomic analysis revealed significant upregulation of multiple metabolic pathways involved in acetyl-CoA (acetyl coenzyme A) synthesis, ensuring an ample supply of precursors for the synthesis of lipophilic products. Furthermore, we observed improved protein synthesis, attributed to UPR activation during the prolonged G1 phase. These findings not only enhanced our understanding and application of yeast's capacity to synthesize lipophilic compounds in applied biotechnology but also offered unique insights into cellular behavior during the modified G1 phase, particularly regarding the UPR response, for basic research. This study demonstrates the potential of G1 phase intervention to increase the yield of hydrophobic compounds in yeast, providing a promising direction for further research.