- Yeast expression systems offer a versatile platform for recombinant protein production, combining many advantages of both prokaryotic and higher eukaryotic hosts.
- Yeasts are unicellular eukaryotes that grow rapidly like bacteria, are easy to genetically manipulate, and can perform several eukaryotic post-translational modifications such as disulfide bond formation, glycosylation, and proper protein folding.
- Among yeast species, Saccharomyces cerevisiae (baker’s yeast) is the most established model, extensively used for both basic research and industrial applications. It is particularly valued for its Generally Recognized As Safe (GRAS) status and its long history of use in food and biotechnology.
- Another important species, Pichia pastoris (now classified as Komagataella phaffii), is widely favored for high-level recombinant protein expression, especially for secreted proteins, due to its strong, tightly regulated promoters and ability to grow to very high cell densities in simple, inexpensive media.
- Yeast systems are capable of expressing complex eukaryotic proteins that would be difficult to produce in bacterial hosts.
- They can introduce certain post-translational modifications, although their glycosylation patterns differ from those found in higher eukaryotes, sometimes limiting their use for producing human therapeutic proteins without additional engineering.
- Proteins can be targeted for secretion into the culture medium, greatly simplifying purification steps compared to intracellular expression.
- The ability to scale up production easily — from small flasks to industrial bioreactors — further makes yeast an attractive host for both academic research and commercial production of enzymes, vaccines, and biopharmaceuticals.
- Despite these advantages, challenges remain.
- Yeast glycosylation can sometimes lead to hypermannosylation, which may affect protein function or immunogenicity.
- Overexpression can also stress the cells, leading to decreased yields or improper protein folding.
- Nevertheless, engineering advances, such as the development of strains with humanized glycosylation pathways or optimized secretion signals, have significantly expanded the utility of yeast expression systems.
- Overall, yeasts represent a powerful and flexible middle ground between the simplicity of bacteria and the sophistication of mammalian cell cultures.
