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 and efficiently traps manganese.
This protein provided an innovative way to test predictions about how proteins acquire metals within cells.
The findings clearly confirm that protein metalation is not automatic when introducing proteins into different cellular environments. Instead, the availability of metals within the cell plays a crucial role, and mismatches can potentially 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 extensive 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 global audience, particularly those in the field of bioengineering, where these insights can be applied to enhance innovative industrial applications, including pharmaceutical development, environmental biotechnology, and biofuel production.
REFERENCE
‘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.
