Engineering yeast to create protein pharmaceuticals

Researchers, headed by Professor Jens Nielsen at Chalmers University of Technology, have successfully mapped out the complex metabolism of yeast cells.

The development is expected to enable scientists to more efficiently produce protein therapies for diseases such as cancer. The findings of the study have been published in an article in Nature Communications.

The market for protein-based therapeutics, pharmaceuticals that mimic the body’s own proteins, is exploding. Some of them are relatively simple to manufacture in yeast-based cell factories. Insulin and HPV vaccine are two that are already under production, but other therapies, such as antibodies to various forms of cancer, are significantly more difficult to manufacture.

“They are currently produced using a cell factory based on a single cell from a Chinese hamster. It’s an extremely expensive process. If we can get yeast cells to do the same thing, it will be significantly cheaper — perhaps 10% of what it costs today. Our vision is to eventually be able to mass-produce and supply the entire world with therapies that are too expensive for many countries today,” said Jens Nielsen, professor of systems biology.

In collaboration with Associate Professor Dina Petrovic and Mathias Uhlén’s research team at the Royal Institute of Technology in Stockholm, Jens Nielsen has been mapping out the complex metabolism of yeast cells for four years.

“We’ve been studying the metabolism of a yeast that we already know is a good protein producer. And we found the mechanisms that can be used to make the process even more efficient. The next step is to prove that we can actually produce antibodies in such quantities that costs are reduced.”

The discussion has mainly been about cancer, but there are many other diseases, for example Alzheimer’s, diabetes and MS, that could potentially be treated by yeast-based protein therapies. How distant a future are we talking about?

“Our part of the process is fast, but pharmaceuticals always take a long time to develop. It could be a possibility in five years, but should absolutely be on the market in 10,” Nielsen said.

Jens Nielsen has recently received three prestigious awards — the Eric and Sheila Samson Prime Minister’s Prize, in Israel, for innovation in alternative fuels for transportation. Nielsen’s award was for contribution to processes for producing hydrocarbons from yeast; the Energy Frontiers Award from the Italian oil company Eni for similar work; he has also been awarded the Royal Swedish Academy of Engineering Sciences (IVA)’s gold medal for innovative and creative research in systems biology.

“Yeast is a superb modelling system. Almost everything in yeast is also found in humans. We have complete computer models of the metabolism of yeast, and we use the same type of models to study human metabolism,” Nielsen explained when he received the IVA award.