S. cerevisiae’s General Stress Response: A tool to save energy and uncouple protein production from growth

Baker’s yeast (Saccharomyces cerevisiae) is used not only in bread, beer, and wine, but also for the production of biofuels and (pharmaceutical) proteins, among others. In these industrial processes, also known as precision fermentation, the products are of value rather than the yeast cells themselves. Therefore, it is relevant to investigate whether yeast cells can be transitioned into a non-growing, yet productive state. When yeast growth slows down, for example due to nutrient limitation, the cells activate the general stress response (GSR).
In this thesis, the role of this GSR is investigated in slow to non-growing yeast. By combining advanced cultivation techniques, including chemostat, fed-batch, and retentostat, with yeast mutants deficient in the general stress response (GSR), this research reveals a new role for the GSR that extends beyond mere stress resistance. Among its various functions, the GSR is central to cellular energetics and survival during periods of extreme nutrient limitation. Furthermore, this work provides a basis for decoupling protein production from growth, thereby increasing the efficiency of precision fermentation processes.