Manchester scientists pave the way for greener cancer treatments

Discovery of new family of ligase enzymes could revolutionize the production of treatments for cancer

9 Jul 2024

Scientists from the University of Manchester have uncovered a more efficient and sustainable way to make peptide-based medicines, showing promising effectiveness in combating cancers.

The Manchester scientists have discovered a new family of ligase enzymes – a type of molecular glue that can help assemble short peptide sequences more simply and robustly, yielding significantly higher quantities of peptides compared to conventional methods. This breakthrough could revolutionize the production of treatments for cancer and other serious illnesses, offering a more effective and environmentally friendly method of production.

The team searched for new ligase enzymes involved in the biological processes that assemble natural peptides in simple bacteria. They successfully isolated and characterized these ligases and tested them in reactions with a wide range of amino acid precursors. By analyzing the sequences of the bacterial ligase enzymes, the team identified many other clusters of ligases likely involved in other peptide pathways

The study provides a blueprint for how peptides, including important medicines, can be made in the future. Following the discovery, the team will now optimize the new ligase enzymes, to improve their output for larger scale peptide synthesis. They have also established collaborations with a number of the top pharmaceutical companies to help with rolling out the new ligase enzyme technologies for manufacturing future peptide therapeutics.

Professor Jason Micklefield, who led the team at The University of Manchester, said, “Using our new ligase enzymes we can produce peptides with promising anti-cancer activity in a single process with excellent yields. Previously, these types of peptides were produced in much lower yields, by a very laborious 10–12 step chemical synthesis process. By combining different ligases together in a single cascade reaction, we can make many different peptides.”

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