Producing biologicals in living expression systems is a big challenge for the Biotech industry. World leaders in the field are betting on a new yield-enhancing expression technology using the yeast Pichia pastoris.

Escherichia coli might be the first bacteria you think about when it comes to biotechnology. However, E. coli is not necessarily the best option to produce recombinant proteins. Its main limitation is its inability to produce postraductional modifications such as glycosylation. Glycosylation is key to producing therapeutic proteins tolerable by human body without antigenic reactions. To this aim, other organisms have been recently used such as Pichia pastoris.

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Pichia Pastoris, source: Igem.org

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Pichia pastoris is a methylotroph yeast, that can grow with the simple alcohol methanol as its only source of energy. Thus, Pichia can easily be grown in cell suspension in reasonably strong methanol solutions that would kill most other micro-organisms, a system that is cheap to set up and maintain.

Another advantage of Pichia pastoris is its similarity to the well-studied Saccharomyces cerevisiae (the baker’s yeast). The two yeast species have similar growth conditions and tolerances, and culturing Pichia pastoris can be readily adopted by labs without specialist equipment.

One important feature of the P. pastoris system is that it is highly suitable for large scale growth and culture using bioreactors . This feature combined with comparatively inexpensive growth medium makes P. pastoris a highly efficient and cost-effective expression system.

pichia pastoris graph

Steps involved in generating and screening P. pastoris clones, from Pichia pastoris as an expression host for membrane protein structural biology, Bernadette Byrne

Pastoris has shown good results in comparison to other expression systems. In a study on over 100 GPCRsn P. pastoris successfully expressed as many individual receptors as a mammalian cell system and produced almost twice as many receptors as Escherichia coli. For several of the receptors, higher functional expression was achieved in P. pastoris compared to the mammalian cell system. Comparison of a receptor expression in P. pastoris and insect cells revealed similar levels of specific activity and binding affinity but the higher cell densities achieved in P. pastoris meant that the overall yield in this system was twice that in the insect cells.

The low cost and high yields together with the eukaryotic processing machinery mean P. pastoris is a viable alternative to insect and mammalian cell systems for the large scale production of many integral membrane proteins for structural studies.

Finally, P. pastoris secretes little endogenous proteins, with ease purification of the protein. All these advantages has positioned Pichia pastoris as a very interesting platform to produce heterologous proteins.

The Big Pharma Boehringer Ingelheim and VTU Technology have bet again on this system, renewing their global Pichia pastoris technology collaboration agreement. VTU Technology, currently offering a very broad and versatile technology platform available for Pichia pastoris protein production, will be responsible for carrying out the joint development program in VTU´s facilities in close collaboration between researchers from both companies. Boehringer Ingelheim has decided to prolong their ongoing technology agreement with VTU to further strengthen Pichia´s position as a highly attractive and competitive host for the production of biopharmaceuticals.

Georg Klima, Executive Director Process Science Austria at Boehringer Ingelheim, said: “We are excited about the continuation of our successful collaboration with VTU Technology. Together we established Pichia pastoris as innovative platform for the manufacture of biopharmaceuticals.

Boehringer Ingelheim is today one of the World leading Contract Manufacturing Organization with huge production facilities in Europe as well as in the US. This partnership could lead Boehringer to integrate this new protein production platform and change the way biologicals are produced.

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