Even when a protein is successfully expressed, perhaps even at a commercially viable titre, there can be undesired products from proteolytic cleavage fragments, post translational modifications (hypermannosylated glycoforms being of particular concern), multimerization or improper folding. Phenotypeca’s toolbox contains solutions to all of these, and our breeding and QTL optimisation can improve on these further.
We choose appropriately from our toolbox and key strain collection the best strains for initial expression and assays. If there are continuous glycoform issues, we can deal with these in a variety of ways. Firstly, if it is not essential for the primary product to be identical to the native protein of interest, sequence modification can be utilised to modify glycosylation sites themselves. If this is not appropriate, our strain development techniques primarily target the knockout of yeast-specific glycosylation and hypermannosylation pathways.
When combined with breeding to downregulate the effects of pathways which cannot be entirely knocked out, this is a powerful approach to reduce the glycosylation of the primary product. Human glycosylation patterns are also in development to facilitate a expand our range of protein expression.
