Yeast could help biopharma cut costs and increase the availability of lifesaving drugs, says the team behind a next-generation expression system based on Saccharomyces cerevisiae. Baker’s yeast has a long history in drug production. One of the first major products made using S. cerevisiae was recombinant human insulin, in a project conducted by researchers at the Novo Research Institute in Denmark in 1987.
Since then, its use has increased. For example, according to one 2017 study, S. cerevisiae-based expression systems are used to manufacture over $40 billion of FDA-approved biologics annually.
But baker’s yeast has yet to reach its full potential, according to Chris Finnis, PhD, intellectual property and projects director at Phenotypeca, who says “First-generation systems were not made widely available by early adopters and broad patent claims restricted their use by industry.”
Addressing these challenges and convincing even more firms to use yeast expression systems is Phenotypeca’s primary goal, according Finnis.
“We have combined the most relevant aspects of expired IP from first-generation yeast systems with modern genetics and yeast breeding techniques to develop a superior next-generation yeast platform for the biopharmaceutical industry,” he tells GEN.
“S. cerevisiae is ‘the model’ eukaryotic system, with a wide range of genetic techniques available for strain optimization and analysis, including methods to understand the fundamental biology of bioprocessing improvements.
“This approach is impossible or impractical for other eukaryotic hosts such as CHO, filamentous fungi, and other yeasts. These methods have been applied to recombinant protein production for the first time by Phenotypeca. This is valuable for IP generation relevant to all eukaryotic expression systems as well as the specific products made by them.”
Engineered S. cerevisiae-based systems have the potential to make a huge range of products—from insulin analogues and albumin-related products to vaccines and antibody fragments.
“Many single non-glycosylated polypeptides are suited to yeast systems, but more complex products with multiple polypeptide chains, cofactors, or glycosylation can also be produced,” notes Finnis. “Surface display, e.g., antibody fragments, and membrane protein expression, is also possible.”
There are also potential advantages on the factory floor.
“The cGMP manufacturing processes are robust and completely animal-free, with no risk from prions or viral pathogens, because S. cerevisiae can grow on simple media comprising only sugars, salts, and vitamins,” points out Finnis. “Baker’s yeast is relatively easy to use for commercial production, including in developing countries. Our focus is optimizing yeast strains for high-productivity low-cost manufacturing applicable to existing bioreactor infrastructure. Novel phenotypes not possible with first-generation yeast systems have also been introduced to enhance sustainability.”