Enzyme engineering has the potential to drive more sustainable and efficient drug manufacturing.

Credit: Nature Synthesis (2024). DOI: 10.1038/s44160-024-00671-w
Researchers have discovered a new way to use biocatalysts to improve the production of critical raw materials needed for essential 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 from the University of Manchester and AstraZeneca have developed a new biocatalytic route that uses enzymes to produce nucleoside analogues. Nucleoside analogs are important ingredients in many medicines used to treat conditions such as cancer and viral infections.
The production of these analogs is typically complex, time-consuming, and generates large amounts of waste. But in a new breakthrough published in the journal Nature Synthesis, researchers say a “biocatalytic cascade” (a series of enzyme-driven reactions) could simplify the process, reduce production time and reduce environmental impact. It has been demonstrated that it is possible to reduce the
“The use of biocatalysts for the development and manufacturing of greener, more sustainable medicines is increasing. Our research aims to replace traditional chemical methods with enzyme-driven reactions to improve the production of complex products. can be produced in an efficient manner.
“With continued development, we hope that this platform will act as a pathway to a wider range of nucleoside-based drugs,” said Matthew Willmott from the Manchester Institute of Biotechnology at the University of Manchester.
Researchers have engineered an enzyme called deoxyribose-5-phosphate aldolase and enhanced its range of functions to treat various sugar-based compounds to serve as building blocks for nucleoside-based medicines, such as oligonucleotide therapeutics. can be generated efficiently.
These building blocks were combined using additional enzymes to develop a condensation protocol for nucleoside analog synthesis. This simplifies the traditional multi-step process to just two or three steps, greatly increasing efficiency.
Further improvements to this method could streamline the production of a wide range of pharmaceutical products while significantly reducing the environmental footprint. The team is currently continuing this research with the Nucleic Acid Therapeutic Accelerator (NATA) manufacturing challenge, aiming to develop sustainable biocatalytic routes to functionalized nucleosides, nucleotides, and oligonucleotides.
Further information: Matthew Willmott et al, An engineered aldolase enables biocatalytic synthesis of 2′-functionalized nucleoside analogs, Nature Synthesis (2024). DOI: 10.1038/s44160-024-00671-w
Provided by University of Manchester
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