Engineered Yeast Strains

About

Yeasts are attractive hosts for the production of heterologous proteins. Their eukaryotic subcellular organization enables them to perform many of the post-translational folding, processing and modification events required to produce “authentic” and bioactive mammalian proteins. In addition, with respect to rapid growth and ease of genetic manipulation, they retain the advantages of a unicellular microorganism. Baker’s yeast, S. cerevisiae, for instance, has wide ranging uses in biotechnology, and production of recombinant protein-based drugs (e.g. insulin, hepatitis vaccine, human papillomavirus particles) is dependent on S. cerevisiae. Due to the importance of this expression vehicle, there are strong economic incentives to increasing S. cerevisiae’s protein production efficiency. Since the profit margin available on exogenously expressed proteins is dependent on protein yield, there is an ongoing search for yeast strains that show enhanced protein yields. The Bms1 gene is believed to play a regulatory role in the biogenesis of the eukaryotic small ribosomal subunit (40S) in yeasts. The 40S subunit is associated with the initiation of protein synthesis in yeasts, and therefore key to increasing protein production. We have discovered that Bms1 up-regulation can significantly improve the production of recombinant proteins in eukaryotic cells. In particular, proteins that are produced at low level in wild-type yeast gain a boost, and all proteins investigated to date have an increased yield of between 5 to 80 fold. This increased yield of recombinant protein may lead to significant cost and efficiency savings for industrial producers of recombinant proteins. In addition to mainstream commercial interests, the we are particularly focused on using this novel yeast expression system to improve expression levels and cellular functionality of G protein-coupled receptors (GPCRs) for drug discovery assays.