Researchers at the Universities of Bristol, Hamburg and London have created bacteria that can access their internal nutrient reserves when they are needed. The results were published in ACS Synthetic BiologyThis will open the door to more robust biotechnologies that are based on engineered microbes.
Synthetic Biology allows scientists the ability to design organisms. This can lead to innovative solutions that range from sustainable production of biomaterials to advanced detection of disease and pathogens.
Dr Thomas Gorochowski, a joint senior author, is a Royal Society University Research Fellow at the School of Biological Sciences in Bristol. He said that many of the engineered biological system we have created are fragile and can break down if they are removed from the controlled lab conditions. This makes it difficult to scale them up.
The team set out to solve this problem by looking at how cells can build up protein reserves when things are good. They then break these down when it is difficult or when additional nutrients are needed.
Klara Szydlo (first author, and a PhD student from the University of Hamburg) elaborated: “Cells need building blocks like amino acid 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 enabled cells to function even in difficult times and made them more resilient to unexpected challenges.
The team engineered bacteria that produced proteins that could not directly be used by cells. However, these proteins were recognized by molecular machine called proteases. These proteases could be called upon to release the amino acid making up the protein reserve when nutrients are fluctuating in the environment. The cells could continue to grow even when the environment did not provide the required nutrients. The system was similar to a biological battery, which the cell could tap into in the event that the mains power is cut.
Dr Gorochowski stated that “developing such a system is difficult because there many different aspects to the design to think about.” How large should the protein reserves be? How quickly should this be broken down? What kind of environmental fluctuations would this approach be able to handle? We had lots to ask and no easy way of evaluating the different options.
The team created a mathematical model to simulate many scenarios and understand the strengths and weaknesses of the system. It was found that the right balance was needed between the size of the protein reserves, the speed at which it is broken down, and the time that nutrients were scarce. The model also showed that cells could be protected from environmental changes if they had the right combination.
Professor ZoyaIgnatova, a joint senior author from University of Hamburg’s Institute of Biochemistry and Molecular Biology, said: “We have been able to show how carefully managing key cellular resources can be a valuable approach for engineering bacteria that needs to operate in difficult environments. This capability will become more important as we deploy our systems in complex real-world settings. Our work helps pave way for more robust engineered cell types that can operate in an safe and predictable manner.
This study was supported by Horizon 2020 research and Innovation program of the European Union under the Marie Skodowska-Curie action, BBSRC, ESPRC and Royal Society.
Source:
MaterialsProvided by University of Bristol. Note: Content can be edited for style or length.