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Addictive cells boost protein production

Addictive cells boost protein production

The biotech start-up company from DTU Biosustain, Enduro Genetics, optimises large-scale fermentation by making the workhorse cells genetically addicted to producing valuable proteins. Their technology boosted yield with 45 percent in a lab scale tank. This could be a game changer for the fermentation industry.

By Anders Østerby Mønsted, Anne Wärme Lykke

Production of proteins for i.e. detergents, feed, membranes, and pharmaceuticals with engineered cells is challenged by cells that do not perform to their maximum. This means great losses with failed fermentations for industries whose bread-and-butter depend on successful protein productions in cell factories.

One problem being that some cells perform very poorly. At least this was the hypothesis stated by the founders of Enduro Genetics, but no one had been able to show it.

By using so-called deep-sequencing and advanced algorithms looking at time-dependent behaviour on cells Enduro Genetics has for the first time identified the rise of 4-5 percent mutated cells, or ‘bad performers’ in a commercial bioprocess over time. This state-of-the-art experiment was performed an industrial 200-liter fermentation tank in the production site of the global water technology company, Aquaporin A/S.

The fact that only 4-5 percent of a population performs poor, might not sound as much. Therefore Enduro Genetics couple growth with performance. This means that cells become addicted to high performance. Hence, bad performers will eventually get wiped out. This trick resulted in a 45% improvement of Aquaporin’s production yield in lab scale because the bad performers were not able to dominate the fermentation.

“This performance optimization is very valuable for all companies working with fermentation processes” says CEO and co-founder of Enduro Genetics and Postdoc at the Novo Nordisk Foundation Center for Biosustainability, DTU, Peter Rugbjerg.

The results startled everyone

Aquaporin A/S manufactures sustainable water filter solutions by fermentation.

Vice President of Membrane Protein Production at Aquaporin, Torsten Bak did not expect this immense production boost using this strategy.

“We were surprised when we obtained a 45% increase in product yield from rescuing what we thought was a minor instability issue. Hopefully, we will be able to use these new insights in our ongoing push to improve production,” says Torsten Bak.

Enduro Genetics’ addiction technology provides an evolutionary incentive to cells that are most productive. This means that fermentations will maintain a higher output over time.

“We clearly find that there is an optimisation opportunity because of this underappreciated cell variation in terms of performance. By working in an industrial setting, we have proved that our technology has commercial potential in biotechnological production,” says CTO and co-founder of Enduro Genetics, Christian Munck.

Even though the collaboration with Aquaporin A/S was very successful, Enduro Genetics is looking to prove their technology further by collaborating with other industrial partners.

source: Technical University of denmark

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