Yeasts are valuable hosts for recombinant protein production, as these unicellular eukaryotes are easy to handle, grow rapidly to a high cell density on cost-effective defined media, often offer a high space-time yield, and are able to perform posttranslational modifications. However, a key difference between yeasts and mammalian cells involves the type of glycosylation structures, which hampers the use of yeasts for the production of many biopharmaceuticals. Glycosylation is not only important for the folding process of most recombinant proteins; it has a large impact on pharmacokinetics and pharmacodynamics of the therapeutic proteins as well. Yeasts' hypermannosylated glycosyl structures in some cases can evoke immune responses and lead to rapid clearance of the therapeutic protein from the blood. This chapter highlights the efforts made so far regarding the glyco-engineering of N- and O-type glycosylation, removing or reducing yeast-specific glycans. In some cases, this is combined with the introduction of humanized glycosylation pathways. After many years of patient development to overcome remaining challenges, these efforts have now culminated in effective solutions that should allow yeasts to reclaim the primary position in biopharmaceutical manufacturing that they enjoyed in the early days of biotechnology.
Recombinant Protein Expression, fungi, Saccharomyces cerevisiae, yeast, Pichia pastoris, N-glycosylation engineering, O-glycosylation engineering
NCBI PubMed ID: 30397726Publication DOI: 10.1007/10_2018_69Journal NLM ID: 8307733Publisher: Springer
Correspondence: Nico.Callewaert@vib-ugent.be
Institutions: VIB-UGent Center for Medical Biotechnology, Ghent, Belgium, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium
Methods: genetic methods
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