ArticleNature synthesis2025
An engineered aldolase enables the biocatalytic synthesis of 2'-functionalized nucleoside analogues.
Article in Nature synthesis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Next-Generation Manufacturing: The Evolving Role of Biocatalysis in AstraZeneca.Chembiochem : a European journal of chemical biology · 2026Review
- Characterization of a Purine Nucleoside Phosphorylase From Colwellia sp. WH041 for Multienzyme Synthesis of Nucleoside Analogs.Chembiochem : a European journal of chemical biology · 2026Article
- A Universal Nucleoside-to-Nucleoside-5'-Triphosphate Enzyme Cascade Driven by Polyphosphate.Angewandte Chemie (International ed. in English) · 2026Article
- Efficient whole-cell biocatalytic synthesis of 2'-deoxy-2'-fluoroadenosine, a key building block for nucleic acid drugs.Synthetic and systems biotechnology · 2026Article
- Improved Nucleoside (2'-Deoxy)Ribosyltransferases Maximize Enzyme Promiscuity while Maintaining Catalytic Efficiency.ACS chemical biology · 2025Article
- An Update: Enzymatic Synthesis for Industrial Applications.Angewandte Chemie (International ed. in English) · 2025Review
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10 authors.
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Abstract
Nucleosides functionalized at the 2'-position play a crucial role in therapeutics, serving as both small-molecule drugs and modifications in therapeutic oligonucleotides. However, the synthesis of these molecules often presents substantial synthetic challenges. Here we present an approach to the synthesis of 2'-functionalized nucleosides based on enzymes from the purine nucleoside salvage pathway. Initially, active-site variants of deoxyribose-5-phosphate aldolase were generated for the highly stereoselective synthesis of d-ribose-5-phosphate analogues with a broad range of functional groups at the 2-position. Thereafter, these 2-modified pentose phosphates were converted into 2'-modified purine analogues by construction of one-pot multienzyme cascade reactions, leading to the synthesis of guanosine (2'-OH) and adenosine (2'-OH, 2'-Me, 2'-F) analogues. This cascade allows for the control of the 2'-functional group alongside 2-stereochemistry. Our findings demonstrate the capability of these biocatalytic cascades to efficiently generate 2'-functionalized nucleosides, starting from simple starting materials.
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