An Austrian consortium reports that they’ve developed the world’s first fully integrated and automated process for producing recombinant proteins using E.coli. Recombinant protein manufacturer enGenes Biotech, the company that led the ECOnti project, says they now have a lab-scale system able to produce significant amounts of Protein A.
According to Juergen Mairhofer, PhD, CEO and co-founder of enGenes, “it was an ambitious project, but we now have a fully functional prototype able to produce a widely used protein.”
The consortium is currently running the prototype at one-liter scale and potentially could have a shipping-container-sized biomanufacturing facility available within two years.
“It’s not far down the line,” he says. “We’re hoping to secure investment to scale up to 10 or 100 liters for our own manufacturing, but we’re always keen to jump into collaborations with others.”
Protein A is used for chromatography and, as such, a crucial part of downstream manufacturing of many monoclonal antibodies. However, Mairhofer explains, continuous automated manufacturing using E.coli cells has traditionally proved hard due to genetic drift and mutations.
“We’ve overcome that using our proprietary enGenes eXpress technology, which allows us to decouple recombinant protein production from cell growth,” he continues. “Our deep knowledge of E.coli means we can play a trick to prevent the cells from undergoing adaptive evolution, a process where they normally prioritize growth over protein production to relieve metabolic burden.”
ECOnti was founded two years ago with funding from Austria’s Research Promotion Agency (FFG). As well as enGenes, the collaboration involved Tosoh Bioscience and several small- and medium-sized enterprises in Austria.
“Many of our collaborators are companies within our ecosystem, either spinouts from our university [University of Natural Resources and Applied Life Sciences (BOKU)] or the Technical University of Graz. There’s a strong focus on Austrian companies and Austrian government funding,” explains Mairhofer. “Our aim is to fit the whole manufacturing site into a small footprint as part of the democratization of bioproduction, and to reduce the ecological impacts of water and chemical use as well.
Benedikt Haslinger, bioprocess modelling engineering at BOKU spinoff company, Novasign, was also involved in the project. As part of his PhD research, he developed a hybrid model to help optimize the continuous process.
“I was working on an end-to-end model to link together upstream and downstream unit operations, and to optimize them in real-time,” he says.
According to Haslinger, the model combined a mechanistic part with equations to describe the physical boundaries of the system, with an artificial intelligence to learn from experimental data.
“The structure we developed was a one-in-all solution enabling both in-silico simulations for process optimization and real-time applications in the lab,” he says. “It was an interdisciplinary endeavor, needing experts from process modeling, automation, and other fields too.”
Haslinger believes the model is flexible, as the data-driven part can be retrained for different cell lines and products, and the mechanistic part can also be easily reconfigured.
“A lot of the workflow can be reused to apply it to a new process quickly. You don’t have to start from scratch,” notes Haslinger, who is now writing up his results ready for publication, along with preparing his PhD thesis.
The post First Fully-Integrated, Automated Production Process for <i>E.coli</i> appeared first on GEN - Genetic Engineering and Biotechnology News.
According to Juergen Mairhofer, PhD, CEO and co-founder of enGenes, “it was an ambitious project, but we now have a fully functional prototype able to produce a widely used protein.”
The consortium is currently running the prototype at one-liter scale and potentially could have a shipping-container-sized biomanufacturing facility available within two years.
“It’s not far down the line,” he says. “We’re hoping to secure investment to scale up to 10 or 100 liters for our own manufacturing, but we’re always keen to jump into collaborations with others.”
Protein A is used for chromatography and, as such, a crucial part of downstream manufacturing of many monoclonal antibodies. However, Mairhofer explains, continuous automated manufacturing using E.coli cells has traditionally proved hard due to genetic drift and mutations.
Preventing cells from undergoing adaptive evolution
“We’ve overcome that using our proprietary enGenes eXpress technology, which allows us to decouple recombinant protein production from cell growth,” he continues. “Our deep knowledge of E.coli means we can play a trick to prevent the cells from undergoing adaptive evolution, a process where they normally prioritize growth over protein production to relieve metabolic burden.”
ECOnti was founded two years ago with funding from Austria’s Research Promotion Agency (FFG). As well as enGenes, the collaboration involved Tosoh Bioscience and several small- and medium-sized enterprises in Austria.
“Many of our collaborators are companies within our ecosystem, either spinouts from our university [University of Natural Resources and Applied Life Sciences (BOKU)] or the Technical University of Graz. There’s a strong focus on Austrian companies and Austrian government funding,” explains Mairhofer. “Our aim is to fit the whole manufacturing site into a small footprint as part of the democratization of bioproduction, and to reduce the ecological impacts of water and chemical use as well.
Benedikt Haslinger, bioprocess modelling engineering at BOKU spinoff company, Novasign, was also involved in the project. As part of his PhD research, he developed a hybrid model to help optimize the continuous process.
“I was working on an end-to-end model to link together upstream and downstream unit operations, and to optimize them in real-time,” he says.
According to Haslinger, the model combined a mechanistic part with equations to describe the physical boundaries of the system, with an artificial intelligence to learn from experimental data.
“The structure we developed was a one-in-all solution enabling both in-silico simulations for process optimization and real-time applications in the lab,” he says. “It was an interdisciplinary endeavor, needing experts from process modeling, automation, and other fields too.”
Haslinger believes the model is flexible, as the data-driven part can be retrained for different cell lines and products, and the mechanistic part can also be easily reconfigured.
“A lot of the workflow can be reused to apply it to a new process quickly. You don’t have to start from scratch,” notes Haslinger, who is now writing up his results ready for publication, along with preparing his PhD thesis.
The post First Fully-Integrated, Automated Production Process for <i>E.coli</i> appeared first on GEN - Genetic Engineering and Biotechnology News.