Abstract
Recombinant expression of therapeutic proteins is one of the major tasks in modern biomedicine. One of the most important factors with respect to therapeutic use in human is posttranslational modifications (PTMs) of the recombinant proteins, of which protein glycosylation is by far the most important to address. Whenever glycosylation has been found to be an important PTM for function or bioactivity, human therapeutics have generally been produced in mammalian Chinese hamster ovary (CHO) cell line. Oglycosylation is one of the most complex regulated PTMs of proteins but also one of the least understood. Currently, mammalian cells are required for human O-glycosylation.
Increasing efforts have been devoted to engineering non-mammalian cells for production of recombinant proteins with “human-like” glycosylation. Substantial success has been achieved with designed N-glycosylation in both lower eukaryotes and even prokaryotes.
Insect and yeast cells produce O-glycosylation incompatible with use in humans,
however recently the yeast Pichia was engineered to perform the first step of human-like O-glycosylation.
This review provides an overview of past and current engineering efforts of N- and Oglycosylation and addresses emerging novel promising platforms such as plants. Plants are safe and low-cost production organisms; they do not perform mammalian-type glycosylation by itself and are easily up-scalable. These features should make it possible to custom design and build capacity for human-like glycosylation in plants
Increasing efforts have been devoted to engineering non-mammalian cells for production of recombinant proteins with “human-like” glycosylation. Substantial success has been achieved with designed N-glycosylation in both lower eukaryotes and even prokaryotes.
Insect and yeast cells produce O-glycosylation incompatible with use in humans,
however recently the yeast Pichia was engineered to perform the first step of human-like O-glycosylation.
This review provides an overview of past and current engineering efforts of N- and Oglycosylation and addresses emerging novel promising platforms such as plants. Plants are safe and low-cost production organisms; they do not perform mammalian-type glycosylation by itself and are easily up-scalable. These features should make it possible to custom design and build capacity for human-like glycosylation in plants
| Original language | English |
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| Publisher | Aarhus University, Faculty of Science and Technology |
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| Number of pages | 128 |
| Publication status | Published - 15 May 2012 |