RESUMEN
Altering the fermentation environment provides an effective approach to optimizing the production efficiency of microbial cell factories globally. Here, lower fermentation temperatures of yeast were found to significantly improve the synthesis and efflux of terpenoids, including glycyrrhetinic acid (GA), ß-caryophyllene, and α-amyrin. The production of GA at 22°C increased by 5.5 times compared to 30°C. Yeast subjected to lower temperature showed substantial changes at various omics levels. Certain genes involved in maintaining cellular homeostasis that were upregulated under the low temperature conditions, leading to enhanced GA production. Substituting Mvd1, a thermo-unstable enzyme in mevalonate pathway identified by transcriptome and proteome, with a thermo-tolerant isoenzyme effectively increased GA production. The lower temperature altered the composition of phospholipids and increased the unsaturation of fatty acid chains, which may influence GA efflux. This study presents a strategy for optimizing the fermentation process and identifying key targets of cell factories for terpenoid production.