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Yeast (e.g. S. cerevisiae, P. pastoris)
A yeast expression system may be a secretion system or an intracellular expression system. Expression levels are generally lower for secretion systems but purification may be facilitated since yeast normally secretes only a small proportion of its own proteins into the growth medium. In contrast to the bacterial expression systems, yeast express proteins with correct N-terminal amino acid residues.
Glycosylation in a yeast system is mainly restricted to the high-mannose oligosaccharide type which means that yeast cannot be considered if the thereapeutic protein contains more complex-type oligosaccharides that are required for biological activity or to prevent a fast clearance of the product from the body.
Even if yeast systems generally show lower expression levels than bacterial systems, there are examples of high-level production, one of the most used is the Pichia pastoris system which offers a cost-effective method for industrial fermentation. This system can produce up to 10 g of protein per litre.
Main validation issue in general is glycosylation pattern.
Advantages
- Well known genetics
- Rapid cell growth (doubles in 90 min)
- Inexpensive culture media
- Secretion systems available
- Provides and facilitates disulfide bond formation and glycosylation
- Relatively few purification problems
Disadvantages
- Heterologous proteins may be incorrectly glycosylated and folded
- Overglycosylation is a risk
- Other posttranslational modifications are limited
- Generally lower expression levels than in bacterial systems
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Read more about how to produce recombinant proteins with bacteria, insect cells, mamalian cells, and transgenics.
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