How do you control for post-translational modifications in yeast to ensure functional equivalence to native human albumin?

Baker’s yeast (Saccharomyces cerevisiae) has been used safely for the manufacture of FDA and EMA approved biologics since the 1980s, including for insulins and vaccines used by billions of patients worldwide. This yeast has co-evolved with humans, being used for thousands of years for bread and fermented drinks consumption. There are even varieties found on tropical fruits, such as S. cerevisiae var. boulardii, which are well known for their beneficial probiotic properties. This makes baker’s yeast an excellent starting point for the manufacture of recombinant human albumin. Because baker’s yeast typically produces ethanol and acetic acid when growing on fruit sugars, it tends not to secrete many proteins of its own, which could complicate the manufacture of biopharmaceuticals. For recombinant albumin production, however, the yeast strains are engineered to minimise the production of specific proteases, which may otherwise degrade some of the albumin they produce. Therefore, compared to other production systems for non-glycosylated biologics such as albumin, the final product from baker’s yeast does not contain unwanted post-translational modifications. This is important because it then becomes easier to purify the final product, which is highly homogeneous, safe and fully functional compared to human-derived albumin, while also being naturally free from the risk of viral and prion contamination.