Engineering the protein secretory pathway of <i>Saccharomyces cerevisiae</i> enables improved protein production

Abstract

Significance Recombinant proteins production by cell factories for medical and industrial use is one of the most prominent achievements in the modern biotech industry. It is constantly necessary to explore the underlying mechanisms of protein secretion to identify new targets for design and construction of improved cell factories. Here, we identified several gene targets, most of which are involved in the trafficking and secretory pathways, that could improve protein production by Saccharomyces cerevisiae to the gram per liter level. We also found that intracellular retention of recombinant proteins can be significantly reduced by engineering the endosome-to-Golgi trafficking. Genes and pathways identified here may provide general guidelines for engineering other cell factories for efficient protein secretion.