Authors
Andrej Ribar, MSc (Technische Universität Graz), Martin Pfeiffer, PhD (Institute for Biotechnology and Bioengineering) and Univ.-Prof. DI DDr. hc Bernd Nidetzky (Technische Universität Graz)
Scientists have developed a highly efficient new method using enzymes – nature’s catalysts – to produce special molecules called C-nucleosides. One important example is pseudouridine, a vital component used in modern mRNA vaccines and therapies, like those for COVID-19. Traditionally, making these molecules can be complex, inefficient, and expensive.
This new approach uses a “cascade” of three enzymes working together in a single pot. It starts with simple, readily available sugars (like ribose) and nucleobases (like uracil). The enzymes first chemically modify the sugar (phosphorylation) and then precisely connect it to the nucleobase, forming the desired C-nucleoside product, pseudouridine 5′-phosphate.
A key innovation is the use of a poorly soluble starting material (uracil) in solid form, allowing the reaction to proceed at much higher concentrations than previously possible, leading to significantly higher output. The process achieves over 90% yield and high productivity (38 grams per liter per hour), making it very efficient. It’s also flexible, capable of producing structural variations of the target molecule by using different starting sugars or nucleobases.
This breakthrough offers a more sustainable and cost-effective route for manufacturing essential building blocks for RNA therapeutics. By harnessing the power of enzymes, this method improves efficiency in industrial biotechnology and contributes to the development of new life-saving medicines.
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Video, Podcast and Image created by AI (2025)