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Researchers at Durham University have achieved a major advancement in understanding how proteins bind metals inside cells, a process crucial to life.
The study, published in Nature Communications, introduces a pioneering approach that allows scientists to accurately predict and engineer the metalation of proteins, a discovery with far-reaching implications for biotechnology and sustainable biomanufacturing.
The research builds upon years of work by the research team, dating back to key discoveries published in 2008.
In the latest study, scientists used a unique protein, originally found in cyanobacteria, which naturally traps manganese.
This protein provided an innovative way to test predictions about how proteins acquire metals within cells.
The findings confirm that protein metalation is not automatic when introducing proteins into different cells. Instead, the availability of metals within the cell plays a crucial role, and mismatches can lead to incorrect metal binding.
For the first time, the team has shown that it is possible to predict and refine which metals bind to proteins by using a specially designed metalation calculator.
This tool enables scientists to forecast metal-protein interactions based on intracellular metal levels.
The research demonstrated how a cyanobacterial manganese-binding protein, when introduced into E. coli, mistakenly binds to iron instead of manganese.
This finding highlights the importance of fine-tuning metal availability when engineering biological systems.
The study also presents practical applications, offering blueprints and calculators to help researchers predict metalation outcomes without needing years of background research.
Lead author of the study Dr Sophie Clough of Durham University said: “This paper was built upon decades of work involving a collaborative effort from a huge number of scientists.
“Now that we have finally tested and validated the models, we hope the blueprints and metalation calculators will be widely used.”
These tools make it easier to engineer metalation processes across a wide range of biological reactions—estimated to include up to half of all enzymatic functions.
Co-author of the study Professor Nigel Robinson of Durham University said: "Half the reactions of life are driven by metals inside cells.
“The blueprints and calculators make it possible for researchers and businesses to engineer these reactions for clean manufacturing."
The study has received funding from UK Research and Innovation (UKRI) and Biotechnology and Biological Sciences Research Council (BBSRC), which have supported the team’s work for over four decades.
The research team is eager to share their findings with a wider audience, particularly those in the field of bioengineering, where these insights can be applied to enhance industrial applications, including pharmaceutical development, environmental biotechnology, and biofuel production.
ENDS
Media Information
Dr Sophie Clough, Professor Nigel Robinson and Dr Peter Chivers from Durham University are available for interview and can be contacted on sophie.clough@durham.ac.uk, nigel.robinson@durham.ac.uk and peter.chivers@durham.ac.uk.
Alternatively, please contact Durham University Communications Office for interview requests on communications.team@durham.ac.uk or +44 (0)191 334 8623.
Source
‘A metal-trap tests and refines blueprints to engineer cellular protein metalation with different elements’, (2025), S. Clough, T. R. Young, E. Tarrant, A. Scott, P. Chivers, A. Glasfeld and N. Robinson, Nature Communications.
An embargoed copy of the paper is available from Durham University Communications Office. Please email communications.team@durham.ac.uk.
Graphics
Associated images are available via the following link: https://www.dropbox.com/scl/fo/oi882f07v12t3tomuqkjg/AMfh9JWOi_BlXviXrdolHng?rlkey=5w6rj8lqvblzx8e7urqzkckcl&st=on0r1ruo&dl=0
About Durham University
Durham University is a globally outstanding centre of teaching and research based in historic Durham City in the UK.
We are a collegiate university committed to inspiring our people to do outstanding things at Durham and in the world.
We conduct research that improves lives globally and we are ranked as a world top 100 university with an international reputation in research and education (QS World University Rankings 2025).
We are a member of the Russell Group of leading research-intensive UK universities and we are consistently ranked as a top 10 university in national league tables (Times and Sunday Times Good University Guide, Guardian University Guide and The Complete University Guide).
For more information about Durham University visit: www.durham.ac.uk/about/
END OF MEDIA RELEASE – issued by Durham University Communications Office.
Journal
Nature Communications