ENGINEERING VACUOLAR SORTING PATHWAYS FOR EFFICIENT SECRETION OF RECOMBINANT PROTEINS

摘要

Recombinant protein production is an expanding branch of biotechnology with increasing economic importance. Currently, 20% of biopharmaceutical proteins and approximately half of the industrial enzymes are produced in yeasts. Many proteins are efficiently secreted by yeast systems, reaching product titers in the g L~(-1) range. The expression of more complex proteins, however, may overwhelm the folding and secretion capacity of the host cells. This triggers the unfolded protein response (UPR), which aims at restoring endoplasmic reticulum (ER) homeostasis. The UPR, in turn, is thought to activate ER-associated protein degradation (ERAD). Alternatively, trafficking of correctly folded proteins can be hampered on their way to the cell exterior leading e.g. to missorting and subsequent degradation in the vacuole.