Enhancing Yeast Surface Display: UPR, ERAD, and ER Dynamics in Recombinant Protein Production.

Over the past two decades, the display of various recombinant proteins on the surfaces of microorganisms, particularly yeast, has garnered significant research attention. This method is rapid, simple and cost-effective, combining the biosynthesis and secretion of recombinant proteins with their immobilization on the host cell surface. Proteins synthesized using this technique are transported to the cell surface and incorporated into the cell wall through mild, native processes, avoiding aggressive chemical immobilization methods that often lead to a loss of physiological activity. Surface-displayed proteins are generally more stable and resistant to environmental changes than those in a solution. Depending on the promoter used, cells can continuously renew the recombinant protein on their surface or express it only under certain conditions. Additionally, cells carrying surface-displayed enzymes can be easily separated from the reaction mixture and reused multiple times. These enzymes can also catalyze reactions with substrates that cannot enter the cells, facilitating extracellular synthesis and simplifying product purification. However, the main obstacle to the industrial application of this method is often low efficiency, resulting in limited amounts of displayed protein. The efficiency depends on the processes that the protein undergoes on its way to the cell surface, following the same pathway as native secretory proteins: synthesis in the endoplasmic reticulum (ER), transport to the Golgi, and delivery to the cell surface