Manchester lab develop more sustainable and rapid route to future medicines

Researchers at The University of Manchester have developed a new powerful and sustainable method of combining enzymes found in nature with non-toxic synthetic catalysts to deliver important chemical building blocks needed for the production of pharmaceuticals as well as other valuable chemicals.

New research published in Nature communications describes the use of natural enzymes and earth-abundant and non-toxic transition metal-catalysts to forge organic molecules, creating what is known as an amide bond, in a more efficient and sustainable manner.

Amide bonds are very important both in natural and non-natural molecules. All living organisms are made up of proteins that are held together by amide bonds which link carbon and nitrogen atoms of amino acid building blocks. Amide bonds are also present in many important pharmaceuticals that help to keep the population healthy, agrochemicals that increase crop yields, and materials such as textiles.

Traditional chemical processes used to create amide bonds are unsustainable, rely on non-renewable ingredients, harmful and wasteful reagents, along with dangerous solvents, all of which lead to difficulties in purification and waste processing. To overcome these problems a team of scientists from the University of Manchester created a new method for combining natural and synthetic catalysts to overcome these issues.

Jason Micklefield Professor of Chemical Biology in the Manchester Institute of Biotechnology (MIB) who led the team said: “We are confident that the integrated approach we have developed can deliver important chemicals using environmentally friendly conditions at an industrial scale.

“We used bacterial cells with enzymes produced inside. Using cells prevents the enzymes coming into contact with the metal catalyst which can cause mutual deactivation. This enables very efficient production of diverse and important amide products.”

Research Fellow and co-author of the study Luis Bering added: “The main advantage is our process can be carried out in water instead of organic solvents that are normally used, which are toxic, flammable, harmful to the user, and damaging to the environment. Additionally, most existing methods are not selective, require multiple steps, and lead to by-products. Our method overcomes these issues, delivering the valuable amides product we need in a clean and high yielding single process.”

The researchers used nitrile hydratase enzymes in combination with non-toxic and earth abundant copper metal catalysts. It is not normally possible to combine these different catalysts as they inactivate each other, hence they are usually used in costly multi-step processes. The team found that by using bacterial cells with the enzyme inside they were able to overcome the compatibility issues and develop an integrated process providing a more direct and environmentally friendly route. The researchers envisage that such integrated processes can revolutionize the way we make molecules for a more sustainable future.

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Bering L, Craven E, Sowerby Thomas S, Shepherd S and Micklefield J. 2022. Merging enzymes with chemocatalysis for amide bond synthesis. Nature Communications, 13(1), 380.