Nucleophilic aromatic substitution (SNAr) is central to the production of many essential products such as medicines and agrochemicals. However, the methods for carrying out this reaction often requires the use of solvents and high temperatures as well as several purification steps.
Now researchers, at the Manchester Institute of Biotechology (MIB) and the Department of Chemistry at the University of Manchester, may have overcome these hurdles with the development of an enzyme which can catalyse SNAR reactions. Their research has been published in the journal Nature.
The enzyme, known as SNAR1.3 came about as the result of work carried out while developing an enzyme for a different chemical process. The researchers found that the initial enzyme exhibited some modest efficiency and selectivity in SNAR reactions. Taking this discovery further and employing automated direct evolution, researchers were able to engineer the enzyme to have the characteristics that they were looking for. The final product was arrived at after evaluating more than 4000 clones.
“This enzyme could be transformative for industry. It not only speeds up a crucial class of chemical transformation, but does so with remarkable precision, even when working with challenging chemical building blocks. This opens up new possibilities for creating complex, valuable molecules with better environmental credentials and lower costs,” said Professor Anthony Green, director of MIB.
Benefits of SNAR1.3 include its sustainability: operating under mild, water-based conditions it reduces the need for more harmful chemicals and energy intensive processes. The enzyme is also versatile, demonstrating efficiency with a wide range of building blocks enabling the creation of complex structures such as quaternary carbon centres, used in advanced drugs. The enzyme also leads to the creation of molecules in a single mirror image form, essential for the safety and effectiveness of medicines.
With the research showing that the SNAR1.3 enzyme holds immense promise as the chemical industry moves towards net-zero and a more sustainable future, there is now a focus on refining the enzyme so that it can catalyse more complex reactions. This would make it a valuable tool in drug development, agricultural chemicals and materials science.
Igor Larrosa, Professor and Chair in Organic Chemistry at the University of Manchester said: “This is a landmark achievement in biocatalysis. It demonstrates how we can harness and even improve on nature’s tools to address some of the toughest challenges in modern chemistry.”
Further reading:
• SCI Sustainability: A new industry-integrated journal for groundbreaking research
• European Commission is called on to incentivise sustainable chemistry
• New research centre tackles green chemistry and clean energy
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