The continued success of protein therapeutics has put a strain on industry's ability to meet the large demand. Creating a more productive expression host for the manufacture of these proteins is a potential solution. Although heterologous proteins are frequently made in organisms as disparate as E. coli and bovines, the single-celled organism S. cerevisiae has emerged as a well-qualified candidate due to its approachable genetic and fermentation attributes as well as its ability to stably fold disulfide bonded and multi domain proteins. Because S. cerevisiae screens for enhanced protein secretion have traditionally utilized low-throughput and often plate-based methods, a high-throughput, liquid phase assay could offer a real advantage in secretory selection. In this thesis, yeast surface display is investigated as a potential proxy for heterologous protein secretion. Although ultimately unsuitable as a screening proxy, the surface display experiments did show a novel method of improving protein secretion by co-expressing a more stably folded protein with the protein of interest. In these studies the secretion of an scFv-Aga2p fusion was stimulated 1 0-fold by the concomitant surface expression of BPTI.
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