Sharing Knowledge: Expressing with Yeast

Why choose a yeast as an expression system?

Yeast-based expression systems, using Pichia pastoris or Saccharomyces cerevisiae hosts for the expression of your recombinant therapeutic proteins can sometimes provide an elegant solution in terms of obtaining expression levels at several grams per liter of soluble, active protein. High cell densities and good volumetric productivities can be achieved with more favorable batch times and cost of goods (COGs) compared to mammalian expression systems.

What are particular challenges of working with Yeast?

Yeast based expression systems can have a propensity to express proteins with clipped N-terminals due to the presence of endogenous proteases but this can be highly protein dependent and sometimes difficult to predict. Saccharomyces sp. in particular can also produce non-native (hyper-mannosylated) glycoproteins. FUJIFILM Diosynth Biotechnologies has extensive experience in performing in depth product characterization to assess product quality. Careful consideration of the pros and cons is necessary but the rewards can be considerable.

What do we bring to your Yeast expressed program?

Once you have settled on yeast as the best expression platform for your product, it is advisable to find a good expression platform with attractive licensing terms.

FUJIFILM Diosynth Biotechnologies has extensive experience with P. pastoris expression systems, in particular with those based on the AOX1 promoter. These expression system provides an attractive option for the production of many proteins, and complements our world leading experience in the process development, scale up and commercialization of yeast-based processes for the production of biopharmaceuticals. Our P. pastoris expression platform is underpinned by our extensive process and analytical development experience.

How do we help?

Our process development experience includes working with MutS, Mut+   strain, secreted and intracellular expressed proteins. cGMP production of bulk drug substance from P. pastoris extends to supporting preclinical and clinical programs as well as commercial requirements. We have extensive experience using solvent feed systems at scale, which are typical needed.

Fujifilm is licensed for the manufacture of bulk drug substance for two commercial products expressed in P. pastoris.