In this review, we address recent advances in yeast synthetic biology with respect to therapeutic recombinant protein production, particularly focusing on genetic tools and host strains suitable for secretory protein production in several yeast expression systems.
Pharmaceutical proteins comprise one of the fastest growing groups of molecular medicines and currently play important roles in the treatment of many diseases.
The production of recombinant therapeutic proteins is one of the fast-growing areas of molecular medicine and currently plays an important role in treatment of several diseases.
Yeasts are unicellular eukaryotic microbial host cells that offer unique advantages in producing biopharmaceutical proteins.
It is noteworthy that in the case of secretory protein expression, strong overexpression might rather lead to lower secretion efficiency due to aggregation of misfolded proteins in the endoplasmic reticulum (ER), as reported in the expression of single-chain antibody fragments, insulin precursor, and α-amylase in ., 2012).
Thus, a set of promoters with different extent of transcriptional activity would be useful to achieve optimal secretion expression.
For example, synthetic promoter libraries have been created through the application of randomized oligonucleotides (Jeppsson ., 2011).
Such diverse sets of constitutive promoters with varied activities and sequences will facilitate the investigation of optimal expression levels of heterologous genes in constructing yeast host strains with heterologous biosynthesis pathway, such as the humanized glycosylation pathway.
The use of yeasts enables an ideal combination of hardy growth on simple media in large-scale bioreactors with the capacity of the desired post-translational modifications and feasibility in genetic manipulations (Mattanovich , make them practical alternative hosts for biotechnological purposes.
The biopharmaceutical products produced in various yeast species, which are on the market or in the final stages of development, are summarized in Table 2.