Maximising protein yields with pichia pastorist

The yeast pichia pastoris is widely used as host for heterologous protein expression for hundreds of different proteins. Recently, the organism has received attention in the biologics industry when the first pichia-derived biopharmaceutical protein received market approval by the FDa. pichia expression cells can furnish yields of more than 10 g/L of secreted recombinant target protein. However, there are many aspects and factors influencing expression levels which have to be tuned properly in order to obtain a high performance expression strain. The yeast Pichia pastoris is widely used as host for heterologous protein expression for hundreds of different proteins. Recently, the organism has received attention in the biologics industry when the first Pichia-derived biopharmaceutical protein received market approval by the FDA. Pichia expression cells can furnish yields of more than 10 g/L of secreted recombinant target protein. However, there are many aspects and factors influencing expression levels which have to be tuned properly in order to obtain a high performance expression strain. The market launch of insulin approximately 30 years ago is generally regarded as the commercial advent of recombinant DNA technology. Since then the biotechnology drugs market has been growing at remarkable rates and the biologics industry is now generating annual revenues of more than $100bn, corresponding to over 15% of the total pharmaceutical market. Today, monoclonal antibodies (mAbs) are the dominating class of proteins on the biologics market. Besides mAbs, other proteins, such as for example cytokines, hormones, blood factors, fusion proteins or therapeutic enzymes, have found pharmaceutical application. As a matter of fact, the diversity of protein molecules developed or marketed by the pharmaceutical industry also reflects certain varieties of molecular architectures and properties. Given the fact that so far the one universal expression host meeting all scientific and commercial requirements for manufacturig of recombinant proteins has not been established, one would conclude that the demand for a considerable variety of protein molecules has to be met by numerous different expression hosts. Nevertheless, from the group of mammalian expression systems Chinese hamster ovary (CHO) cells are the dominating technology, and on the microbial side, this role is occupied by Escherichia coli. These two expression systems have truly become the main workhorses of the industry, and are much appreciated by their well established performance and safety profiles. Roughly 30 to 40% of all biologics are produced in microbial organisms, and besides E. coli, yeasts such as Saccharomyces cerevisiae, Hansenula polymorpha and Pichia pastoris have found some application.