Abstract
Yeast and other fungal protein-expression hosts have been extensively used to produce industrial enzymes, and are often the expression system of choice when manufacturing costs are of primary concern. However, for the production of therapeutic glycoproteins intended for use in humans, yeast have been less useful owing to their inability to modify proteins with human glycosylation structures. Yeast N-glycosylation is of the high-mannose type, which confers a short half-life in vivo and thereby compromises the efficacy of most therapeutic glycoproteins. Several approaches to humanizing yeast N-glycosylation pathways have been attempted over the past decade with limited success. Recently however, advances in the glycoengineering of yeast and the expression of therapeutic glycoproteins with humanized N-glycosylation structures have shown significant promise — this review summarizes the most important developments in the field.
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Acknowledgements
The authors are grateful to the outstanding scientists that provided the basic knowledge upon which the engineering of humanized yeast strains was made possible. In particular, we wish to express our gratitude to P. Robbins, R. Bretthauer, K. Moremen, C. Barlowe, M. Aebi and R. Hitzman for helpful discussions and support. Most importantly, we are grateful to the exceptional group of scientists we have been able to work with over the past four years. It is their work that has advanced the field in such a significant way and may lead to a paradigmatic change in the production of complex protein-based therapeutics.
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Wildt, S., Gerngross, T. The humanization of N-glycosylation pathways in yeast. Nat Rev Microbiol 3, 119–128 (2005). https://doi.org/10.1038/nrmicro1087
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DOI: https://doi.org/10.1038/nrmicro1087
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