Scientists engineer bacteria to cope in challenging environments

Date:
February 22, 2022
Source:
University of Bristol
Summary:
Researchers have engineered bacteria with internal nutrient reserves
that can be accessed when needed to survive extreme environmental
conditions.

The findings pave the way for more robust biotechnologies based
on engineered microbes.



FULL STORY ========================================================================== 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 findings, published
in ACS Synthetic Biology, pave the way for more robust biotechnologies
based on engineered microbes.


========================================================================== Synthetic Biology allows scientists to redesign organisms, harnessing
their capabilities to lead to innovative solutions spanning the
sustainable production of biomaterials to advanced sensing of pathogens
and disease.

Dr Thomas Gorochowski, joint senior author and a 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." To tackle this problem, the team focused on the idea of
building up reserves of protein within cells when times are good, and
then breaking these down when conditions are difficult and additional
nutrients are needed.

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 have a protected reserve of these
that could then be broken down and released when nutrients became scarce
in the wider environment. This allowed the cells to continue functioning
when times were tough and made them more robust to any unexpected
challenges they faced." To create such a system, the team engineered
bacteria to produce proteins that could not be directly used by the cell,
but which were recognized by molecular machines called proteases. When nutrients fluctuated in the environment, these proteases could then be
called on to release the amino acids making up the protein reserve. The released amino acids allowed the cells to continue growing, even though
the environment lacked the nutrients required. The system acted similar
to a biological battery that the cell could tap into when the mains
power was cut.

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 reserve be? How quickly does this need to
be broken down? What sorts of environmental fluctuation would this
approach work for? We had lots of questions and no easy way to assess
the different options." To get around this problem, the team built
a mathematical model that allowed them to simulate lots of different
scenarios and better understand where the system worked well and where
it broke. It turned out that a careful balance was required between the
size of the protein reserve, the speed of its breakdown when required, and
the length of time nutrients were scarce. Importantly though, the model
also showed that if the right combination of these factors was present,
the cell could be completely shielded from changes in the environment.

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 Sk?odowska-Curie Action, BBSRC, ESPRC,
and the Royal Society.

========================================================================== Story Source: Materials provided by University_of_Bristol. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Klara Szydlo, Zoya Ignatova, Thomas E. Gorochowski. Improving the
Robustness of Engineered Bacteria to Nutrient Stress Using
Programmed Proteolysis. ACS Synthetic Biology, 2022; DOI:
10.1021/acssynbio.1c00490 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220222135239.htm

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