Development of second-generation S. cerevisiae hosts for enhanced protein yield and quality

Recombinant protein expression is the keystone manufacturing technique supporting production of many biological therapies. A large number of protein expression systems exist, but the majority of biological drugs and protein products that are approved for clinical use have been manufactured using mammalian cell culture techniques. These manufacturing processes are laborious, slow, and expensive.

Yeast systems offer a significantly simpler way of expressing recombinant proteins at scale compared to mammalian cell culture, and at a greatly reduced cost.

A number of yeast protein expression systems have been commercialised. However, the baker's yeast (Saccharomyces cerevisiae) expression systems, which are most commonly used in industry for biologics production, have never themselves been widely commercialised by the companies that developed them. The patent protection for these baker's yeast systems has now expired or is expiring. This engenders considerable freedom to create new systems and develop new IP surrounding enhanced, second-generation protein expression systems utilising S. cerevisiae as their protein-production powerhouse and making this technology widely available to new companies wishing to bring recombinant products to the market.

The project will enable Phenotypeca to develop novel strains of S. cerevisiae to be created that can be quickly and easily tailored to optimize production of recombinant proteins.

In this instance, the platform will be exemplified by producing a protein (H-Guard) for another UK SME - Invizius - which is a coating used on dialysis equipment to prevent inflammatory responses induced by repeated exposure to dialyser membranes.

Invizius will work alongside the Centre for Process Innovation (CPI), who join the consortium as grant funded partners to conduct industrial fermentation modelling to identify the most suitable for scale-up production.

The project supports Phenotypeca to become a service provider for clients wanting S. cerevisiae-based protein expression systems. There are currently no commercial providers of industrial S. cerevisiae systems -- all S. cerevisiae systems used industrially are proprietary systems developed in-house by other companies who don't want to share their technology of offer a development service. Phenotypeca is attempting to overcome the unmet market need for S. cerevisiae protein expression systems, especially for a class of therapeutic peptides for which Pichia pastoris-based yeast systems cannot meet the quality and regulatory requirements.