Newswise — Researchers from the Universities of Bristol and Hamburg have engineered bacteria with internal nutrient reserves that can be accessed when needed to survive extreme environmental conditions. The results were published in ACS Synthetic BiologyThis will open the door to more robust biotechnologies that are based on engineered microbes.
Synthetic Biology is a way for scientists to create new organisms. They can harness their capabilities to produce innovative solutions, from the sustainable production and monitoring of pathogens and disease to the advanced sensing of them.
Dr Thomas Gorochowski, joint senior author, and Royal Society University Research Fellow in The School of Biological Sciences at Bristol, said: “Many of the engineered biological systems we have created to date are fragile and break easily when removed from the carefully controlled conditions of the lab. This makes their deployment and scale-up difficult.”
The team looked at the problem from two perspectives: first, building up protein reserves in cells when times are good and then breaking them down when conditions are tough or additional nutrients are required.
Klara Szydlo, first author and a PhD student at the University of Hamburg, elaborated: “Cells require building blocks like amino acids to function and survive. We modified bacteria to create a protected reserve of amino acids that could be used to break down and release nutrients when they were scarce. This allowed the cells to continue functioning when times were tough and made them more robust to any unexpected challenges they faced.”
The team engineered bacteria to produce proteins that could be used by the cells, but were recognized by molecular machines known as proteases. These proteases can then be called upon to release amino acids from the protein reserve, even if nutrients are changing in the environment. The cells could continue to grow even when the environment did not provide the required nutrients. The system worked in a similar way to a biological battery that the cells could tap into if the mains power was interrupted.
Dr Gorochowski added: “Developing such a system like this is difficult because there are many different aspects of the design to consider. How large should the protein reserves be? How fast should this be broken down? This approach could be used for various types of environmental fluctuation. We had lots of questions and no easy way to assess the different options.”
The team devised a mathematical model that would allow them to simulate many different scenarios and help them understand why the system works and what it doesn’t. It was discovered that there was a delicate balance between the size and speed of protein breakdown, as well as the amount of nutrients available. Importantly, however, the model showed that the cell could be totally protected from environmental changes if all of these factors were present.
Professor Zoya Ignatova, joint senior author from the Institute of Biochemistry and Molecular Biology at the University of Hamburg, concluded: “We’ve been able to demonstrate how carefully managing reserves of key cellular resources is a valuable approach to engineering bacteria that need to operate in challenging environments. This capability will become increasingly important as we deploy our systems into complex real-world settings and our work helps pave the way for more robust engineered cells that can operate in a safe and predictable manner.”
This study was funded by the European Union’s Horizon 2020 research and innovation program under the Marie Skodowska-Curie Action, BBSRC, ESPRC, and the Royal Society.
Paper:
‘Improving the robustness of engineered bacteria to nutrient stress using programmed proteolysis’ by Klara Szydlo, Zoya Ignatova and Thomas E. Gorochowski in ACS Synthetic Biology.