February 1, 2009 (Vol. 29, No. 3)
Novozymes, formerly part of NovoNordisk, bases much of its contract manufacturing capability on yeast-based expression, which it believes to be the gold standard in microbial protein expression, according to Dermot Pearson, marketing director. NovoNordisk’s experiences in biomanufacturing have enabled Novozymes to move rapidly into the biomedical arena.
Yeast sports many positive features for biomanufacturing. “We can push CHO mammalian cells to produce more than a gram per liter of protein a day, but this requires long growth cycles,” Pearson continues, “whereas with yeast you can achieve five grams per liter per day using inexpensive media.”
Other advantages include the fact that yeast secretes protein into the medium and users do not have to deal with inclusion bodies or endotoxins. “For proteins that don’t require glycosylation, yeast is ideal,” Pearson adds, “but we have also engineered yeast strains so they are deficient in both n-linked and o-linked glycosylation.”
Novozyme has aggressively developed albumin fusion technology, joining albumin to various therapeutic molecules to improve their delivery. A prime example is Albuferon, constructed by linking albumin to interferon alpha. “With our technology we get exceptional expression,” Pearson states.
Because yeast has been employed for industrial purposes for so long in the manufacture of food and alcoholic beverages, there is a great repository of engineering knowledge available on mega-large-scale manufacturing. While thousands of liters are routinely handled in the biotechnology industry, winemaking dwarfs these figures, with behemoth fermentors in the range of hundreds of thousands of liters. This level of upscaling could provide massive yields of product if such feats of production are required.