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Researchers at the University of Tartu’s Institute of Technology are developing an innovative antibiotic-free method for protein production by engineering bacteria with a temperature-controlled switch. The approach shows strong potential at the lab scale and could reduce environmental impact, but the next challenge is optimizing it for large-scale manufacturing.
Every person has taken antibiotics as medicine. The problem is that antibiotics are also used massively in the protein production industry. Proteins such as insulin for diabetes, vaccines like the Hepatitis B antigen, and various food enzymes are often produced using bacteria. To produce protein, we need to use bacteria. To keep the process ongoing inside the bacteria, we need to use antibiotics.
So how does that work? Bacteria are like a tiny factory making proteins. Inside each factory is an instruction manual– a circular piece of DNA that tells the bacteria what to make. Antibiotics act like security guards, protecting that manual. If antibiotics are not present when the cells are growing, the manual gets lost, and the protein production does not happen properly. Without them, bacteria lose the instructions and stop producing.
What’s the problem if we keep using antibiotics? It’s just not one or two pills of antibiotics. Industries add kilograms of antibiotics to help bacteria make those proteins. A single industrial 50-ton bioreactor consumes as many antibiotics in a year as 100,000 people — roughly the entire population of Tartu, the second biggest city in Estonia. Moreover, one factory may operate several bioreactors, and that’s just one facility. This shows how enormous the antibiotic demand in the biotech industry really is.1
So, it’s not only expensive but wasteful, and harmful. This practice not only increases production costs but also creates antibiotic pollution and drives antimicrobial resistance, a global health crisis that already kills millions every year.
In Ritu Ghosh´s research, she is trying to solve the problem through genetic engineering. She placed the protein’s manual inside the bacteria’s main DNA (chromosome), so then the bacteria grow there and are safely stored in their “main office.” The bacteria grow normally without antibiotics. Then, when it’s time to produce, they simply flip a switch — by raising the temperature from 30°C to 37°C.
This temperature switch tells the bacteria first to cut the instruction manual from the office and move it to the assembly line — forming a small DNA circle. Then they start making more copies of the small DNA circle and start producing protein at full speed. At the same time, it also tells the bacteria to stop their own growth. Now the bacteria are not growing, active and putting all its energy into protein production. In the lab, in this way, the researchers are producing the protein using zero antibiotics. Ritu Ghosh feels this can be a sustainable future for protein production on a large scale.
Switching to an antibiotic-free production process is quite complex. The research group has published a paper that explains how this switching process works.2 There have been many attempts to develop antibiotic-free production methods. While these approaches show good potential at the lab scale, it’s still challenging to optimize them for large-scale or industrial production. Their research has already patented the switching process, and Ritu Ghosh is currently working on improving and optimizing it further.
In short: Grow safely → Flip the switch → Produce efficiently.
Presentation in the 3-minute Thesis Competition
This article is written by Ritu Ghosh, who is a Junior Research Fellow in Molecular Biotechnology at the University of Tartu´s Institute of Technology and was written as part of the 3-Minute Thesis Competition.
- Kõnnussaar, T. (2023). Ülikooli molekulaarbioloogid tõid valgutootmisse käiguvahetuse.Universitas Tartuensis. https://ut.ee/et/sisu/ulikooli-molekulaarbioloogid-toid-valgutootmisse-kaiguvahetuse ↩︎
- Kasari, M., Kasari, V., Kärmas, M., & Jõers, A. (2022). Decoupling growth and production by removing the origin of replication from a bacterial chromosome. ACS Synthetic Biology, 11(8), 2610–2622. https://doi.org/10.1021/acssynbio.1c00618 ↩︎
