Yeast display

Yeast display, also known as yeast surface display, is the expression of a desired antibody or protein on the cell surface of yeast, using recombinant protein technology. Yeast display is performed in Saccharomyces cerevisiae for the purpose of isolating and engineering antibodies or proteins for the development of therapeutics and for other biomedical and biotechnology applications. Yeast display is one type of cell surface display among other techniques that use bacteria cells, mammalian cells, and insect cells. In addition, other molecular display platforms have been developed for protein engineering in which proteins are tethered to ribosomes, mRNA, or on the surface of phage (phage display).

The process for yeast display and other types of cell surface display is the introduction of recombinant DNA with a protein of interest fused to a cell-surface anchor protein. The anchor protein contains signal sequences that direct the transport of the fusion protein to the cell surface. A glycosylphosphatidylinositol (GPI) attachment signal tethers the recombinant protein to the cell wall. Since yeast and mammal cells are both eukaryotic cells, certain protein processing steps are similar, such as post-translational modifications and disulfide bond formation. Cell surface anchor proteins used in yeast display include Agα1p, Aga2p, Cwp1p, Cwp2p, Tip1p, Flo1p, Sed1p, YCR89w, and Tir1.

When yeast display is used in protein engineering applications, a protein library is generated using genetic material that codes for protein variants. Libraries of protein variants are screened for desired characteristics (phenotype), such as the affinity of the protein for its binding partner, and the genotype that produced the desired phenotype is identified by DNA sequencing. Genotype-phenotype coupling is the coupling of the protein variant to its genetic information. Fluorescence-activated cell sorting (FACS) is often used for the selection of phenotype in yeast display.

Yeast display was used to develop the PD-1 blocking antibody Sintilimab, approved in China for the treatment of Hodgkin’s lymphoma.

Yeast display can be used to display peptides, short chains of amino acids that have the potential to treat disease. Many peptide-based drugs have been approved, and there is a growing interest in peptide screening for bioactive peptides against specific targets. Combination approaches use both yeast display and phage display.

Yeast display can be used to identify peptide ligands recognized by T cells (peptide-MHC binding) not identified by computational prediction in a high-throughput manner. The approach could be useful for T cell-directed therapeutics and for the identification of immune interventions.