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Enzyme technology has the potential to advance more sustainable and efficient drug production

Credit: Nature Synthesis (2024). DOI: 10.1038/s44160-024-00671-w

Researchers have found a new way to use biocatalysis to improve the production of critical raw materials for vital medicines, making the process faster, more efficient and more environmentally friendly. Biocatalysis is a process that uses enzymes as natural catalysts to carry out chemical reactions.

Scientists at the University of Manchester and AstraZeneca have developed a new biocatalytic pathway that uses enzymes to produce nucleoside analogues, which are important components of many medicines used to treat diseases such as cancer and viral infections.

Typically, the production of these analogs is complicated, time-consuming, and generates significant waste. However, in a new breakthrough, published in the magazine Nature SynthesisThe researchers have shown how a “biocatalytic cascade” – a series of enzyme-controlled reactions – can simplify the process and potentially shorten production time and reduce environmental impact.

“The use of biocatalysis for greener and more sustainable drug development and manufacturing is increasing. Our work shows that by replacing traditional chemical methods with enzyme-controlled reactions, we can produce complex products efficiently.”

“We hope that with further development this platform will serve as a route to a wider range of nucleoside-based medicines,” says Matthew Willmott from the Manchester Institute of Biotechnology at the University of Manchester.

The researchers developed an enzyme called deoxyribose-5-phosphate aldolase and expanded its functional spectrum to efficiently produce various sugar-based compounds that serve as building blocks for nucleoside-based drugs, such as oligonucleotide therapeutics.

These building blocks were combined using additional enzymes to develop a condensed protocol for the synthesis of nucleoside analogs that simplifies the traditional multi-step process to just two or three steps, significantly improving efficiency.

With further refinement, this method could help streamline the production of a wide range of drugs while significantly reducing their environmental footprint. The team is now continuing this work with the Nucleic Acid Therapeutic Accelerator (NATA) manufacturing challenge, which aims to develop sustainable biocatalytic pathways for functionalized nucleosides, nucleotides and oligonucleotides.

Further information:
Matthew Willmott et al.: An engineered aldolase enables the biocatalytic synthesis of 2′-functionalized nucleoside analogues. Nature Synthesis (2024). DOI: 10.1038/s44160-024-00671-w

Provided by the University of Manchester

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