Increase the resistance of engineered bacteria to stress nutrients

Green fluorescent protein (shown in the middle) is used by engineered bacteria as a reserve of amino acids. When nutrients become low, protein can be broken down to provide essential amino acids needed for survival. Author: Clara Szydla and Thomas Gorokhovsky

Researchers from the Universities of Bristol and Hamburg have created bacteria with internal nutrient stores that can be accessed when needed to survive in extreme environmental conditions. Conclusions published in Synthetic Biology ACSpave the way for more reliable biotechnologies based on engineered microbes.

Synthetic biology allows scientists to redesign organisms using their capabilities to lead to innovative solutions that encompass sustainable biomaterial production and advanced detection of pathogens and diseases.

Dr Thomas Gorokhovsky, co-senior author and researcher at the Royal Society University at the School of Biological Sciences in Bristol, said: “Many of the engineers biological systems We have created to date fragile and easily breakable when removed from carefully controlled laboratory conditions. This makes it difficult for them to deploy and expand. “

To solve this problem, the team focused on the idea of ​​building up reserves protein inside cells if the times are good, then break them down if conditions are difficult and extra nutrients are needed.

Clara Szydla, first author and doctor of philosophy. a student at the University of Hamburg, explained: “Cells need building blocks like amino acids function and survive. We modified the bacteria to have their protected reserve, which could then be broken down and released if the nutrients become deficient within wide limits. environment. This allowed the cells to continue to function in difficult times and made them more resilient to any unexpected problems they encountered. “

To create such a system, the team developed bacteria to produce proteins that could not be used directly by the cell, but which were recognized by molecular machines called proteases. When nutrients fluctuate in the environment, these proteases can be caused to release the amino acids that make up the protein supply. The released amino acids allowed the cells to continue to grow even when the environment lacked the necessary nutrients. The system operated similarly to a biological battery, to which the cell could connect when the mains was disconnected.

Dr. Gorakhovsky added: “Developing a system like this is difficult because you have to consider many different aspects of design. How big should the protein supply be? How fast should it be broken down? What kinds of environmental fluctuations can this approach work? We had a lot of questions and there was no easy way to evaluate the different options. “

To circumvent this problem, the team built a mathematical model this 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 reserve, the rate of its cleavage if necessary, and the length of time when nutrients were deficient. Importantly, however, the model also showed that with the right combination of these factors, the cell can be completely protected from changes in the environment.

Professor Zoya Ignatova, co-author of the Institute of Biochemistry and Molecular Biology at the University of Hamburg, concluded: “We have been able to demonstrate how careful management of key cellular resources is a valuable approach to engineered bacteria that have to work in challenging environments. This capability will become increasingly important as we deploy our systems in challenging real-world environments, and our work helps pave the way for more robust engineering cells that can operate safely and predictably. ”

How to meet the demand for bacterial “factories”

Additional information:
Clara Szydla et al., Increasing the resistance of engineered bacteria to nutritional stress through programmed proteolysis, Synthetic Biology ACS (2022). DOI: 10.1021 / acssynbio.1c00490

Citation: Improving the resilience of designed bacteria to nutrient stress (2022, February 21) obtained February 21, 2022 from

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