Researchers from the universities of Bristol and Hamburg have engineered bacteria with internal stores of nutrients accessible when needed to survive extreme environmental conditions. The findings, published in ACS Synthetic Biologypave the way for more robust biotechnologies based on modified microbes.
Synthetic biology allows scientists to redesign organisms, harnessing their capabilities to achieve innovative solutions ranging from the sustainable production of biomaterials to the advanced detection of pathogens and diseases.
Dr Thomas Gorochowski, co-lead author and researcher at the Royal Society University in Bristol’s School of Biological Sciences, said: “Many of the modified biological systems we have created to date are fragile and break easily when removed from carefully controlled laboratory conditions. This makes deploying and scaling them difficult.
To solve this problem, the team focused on the idea of building up reserves of proteins in cells when things are going well, then breaking them down when conditions are tough and extra nutrients are needed.
Klara Szydlo, first author and PhD student at the University of Hamburg, explained: “Cells need building blocks like amino acids to function and survive. We engineered bacteria to have a protected storehouse of these that could then be broken down and released when nutrients became scarce in the larger environment.This allowed cells to continue functioning when times were tough and made them more robust in the face of any unexpected challenges they faced.
To create such a system, the team engineered bacteria to produce proteins that could not be used directly by the cell, but were recognized by molecular machines called proteases. When nutrients fluctuated in the environment, these proteases could then be called upon to release the amino acids that make up the protein reserve. The released amino acids allowed the cells to continue to grow, even if the environment lacked the necessary nutrients. The system acted as a biological battery that the cell could draw on when mains power was lost.
Dr Gorochowski added: “Developing such a system like this is difficult because there are many different aspects of the design to consider. How big should the protein store be? How fast should it be broken down? We had a lot of questions and there was no easy way to assess the different options.”
To circumvent this problem, the team built a mathematical model that allowed them to simulate many different scenarios and better understand where the system worked well and where it broke. It turned out that a careful balance was needed between the size of the protein pool, the speed of its degradation when needed, and the length of time nutrients were scarce. Importantly, the model also showed that if the right combination of these factors were present, the cell could be completely protected from changes in the environment.
Professor Zoya Ignatova, co-lead author from the Institute of Biochemistry and Molecular Biology at the University of Hamburg, concluded: “We were able to demonstrate how the careful management of stores of key cellular resources is a valuable approach. to engineer bacteria that must function in harsh environments.This capability will become increasingly important as we deploy our systems in complex real-world environments and as 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 Skōdodowska-Curie Action, BBSRC, ESPRC and the Royal Society.
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