Enduro Sense Boosts Cell Productivity by 30% in Biomanufacturing

In the intricate world of biomanufacturing, a fundamental challenge has persisted: maintaining high productivity in microbial cells over extended periods. Christian Munch, CEO of Enduro Genetics, recently highlighted this issue at the SynBioBeta conference, noting that in any bioreactor, only a small percentage of cells reliably produce their engineered target products. The remaining cells, termed “freeloaders,” consume valuable resources without contributing to production, thereby complicating the economics of industrial fermentation.

“Sometimes only 15-20% of the cells are responsible for producing your target product. And after 60-80 generations, the cells may completely lose the ability to produce,” explained Munch, who brings extensive experience from his tenure at Novozymes. The problem, he said, lies in the natural evolutionary tendencies of microbial cells, which do not inherently benefit from producing engineered substances like dairy proteins or vaccines. Over time, mutant cells that abandon production in favor of faster growth tend to dominate, leading to a significant drop in overall productivity.

Addressing this issue head-on, Enduro Genetics, a Copenhagen-based startup, has developed a groundbreaking solution known as “Enduro Sense.” This technology, co-developed by Dr. Peter Rugbjerg and Dr. Christian Munck at the Technical University of Denmark, effectively “tricks” cells into linking their survival with the production of the target substance. By coupling essential genes with high production of the target substance, only cells that produce the desired output can thrive and proliferate.

“Our solution [‘Enduro Sense’] is a genetic biosensor that couples with essential genes in the cell and that means that only cells that are high-producers of the target substance can grow or proliferate,” Munch elaborated. “The essential genes are upregulated when the cell produces the target substance and downregulated when they don’t.” This approach ensures that high-producing cells dominate the bioreactor, sustaining bioproduction over longer time scales and improving yields by over 30%.

Enduro Sense has already been tested across various strains, including E.Coli, Bacillus, baker’s yeast, and filamentous fungi, producing diverse products from milk proteins to antibodies. The technology’s flexibility allows it to work independently of the product pathway and with both intracellular and extracellular expression systems.

The implementation of Enduro Sense is straightforward and requires no changes to the media or production process. It begins with an analysis of fermentation samples using RNA-seq and Enduro’s proprietary algorithm. The company then designs sensor-essential gene constructs, which can be integrated into the production strain either by Enduro or the client. This process ensures that the highest-producing cell variants dominate, leading to significantly more productive biomanufacturing.

Munch is optimistic about the technology’s potential, stating, “We’re kind of putting everything in reverse. Right now there is a selective evolutionary pressure against high-producing cells because it places a burden on them. With our tech, we’re reversing that so high-production confers an evolutionary benefit.”

One compelling study conducted by Enduro cofounder Dr. Rugbjerg demonstrated that a production organism retained high-yield mevalonic acid production through 95 generations of cultivation, far outlasting the regular strain, which ceased production. This highlights the potential for Enduro Sense to revolutionize biomanufacturing by maintaining high productivity over extended periods.

Enduro Genetics, which secured seed funding from NOON Ventures in 2022 and grant funding from the European Innovation Council (EIC), is now seeking to raise a series A round. The company operates on a licensing and royalty model, positioning itself as a tools company rather than a product company. Munch emphasized that the technology addresses universal challenges in biomanufacturing, making it a game-changer for industries ranging from vitamins to antibiotics.

As Enduro Genetics continues to forge partnerships with leading industry players, the biomanufacturing sector may soon witness a significant shift towards more efficient and sustainable production processes.

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