Yeast are capable recombinant protein expression hosts that provide eukaryotic posttranslational modifications such as disulfide bond formation and N-glycosylation. This property has been used to create surface display libraries for protein engineering; however, yeast surface display (YSD) with common laboratory strains has limitations in terms of diversifying glycoproteins due to the incorporation of high levels of mannose residues which often obscure important epitopes and are immunogenic in humans. Developing new strains for efficient and appropriate display will require combining existing technologies to permit efficient glycoprotein engineering. Foundational efforts generating knockout strains lacking characteristic hypermannosylation reactions exhibited morphological defects and poor growth. Later strains with "humanized" N-glycosylation machinery surmounted these limitations by targeting a small suite of glycosylhydrolase and glycosyltransferase enzymes from other taxa to the endoplasmic reticulum and Golgi. Advanced yeast strains also provide key modifications at the glycan termini that are essential for the full function of many glycoproteins. Here we review progress toward glycoprotein engineering when glycosylation is required for full function using advanced yeast expression platforms and the suitability of each for YSD of glycoproteins.

• PMID: 34611870
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Reference Type

Journal Article | Review

Authors

Shenoy A, Barb AW

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