The Absence of Sec72 Reshapes Yeast Cell Functions to Increase Protein Secretion

Protein secretion plays a crucial role in numerous biological processes, yet its underlying mechanisms remain incompletely understood. This study investigates the role of Sec72, a component of the Sec complex in Saccharomyces cerevisiae , in protein targeting and translocation to the endoplasmic reticulum. We discovered that deleting SEC72 significantly enhances the secretion of proteins with strongly hydrophobic signal peptides (SPs), accompanied by observable changes in cellular functions, such as iron homeostasis, cell wall assembly, and protein synthesis. Importantly, we identified specific gene modifications that, in combination with SEC72 deletion, enable a yeast strain to secrete α-amylase up to 6.5 g/l in fed-batch fermentation. These findings deepen our understanding of SP-mediated protein translocation and provide a basis for optimizing yeast hosts for more effective protein production.