ArticleNature communications2023
A selective and atom-economic rearrangement of uridine by cascade biocatalysis for production of pseudouridine.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 29 citations in OpenAlex.
- Systematic metabolic engineering ofSynthetic and systems biotechnology · 2026Article
- 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 combined pseudouridine biomanufacturing platform enabled by a streamlined designer pathway.Nature communications · 2025Article
- N- to C-Glycoside Rearrangement of Uridine 5'-Phosphate in Two Enzymatic Steps for the Production of Pseudouridine 5'-Phosphate.Biotechnology and bioengineering · 2025Article
- Integrated Chemoenzymatic Synthesis of the mRNA Vaccine Building Block NAngewandte Chemie (International ed. in English) · 2025Article
- An Update: Enzymatic Synthesis for Industrial Applications.Angewandte Chemie (International ed. in English) · 2025Review
- Snapshots of the Reaction Coordinate of a Thermophilic 2'-Deoxyribonucleoside/ribonucleoside Transferase.ACS catalysis · 2024Article
- Molecular Dynamics and Docking Simulations of Homologous RsmE Methyltransferases Hints at a General Mechanism for Substrate Release upon Uridine Methylation on 16S rRNA.International journal of molecular sciences · 2023Article
- Metabolic Engineering ofACS omega · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a crucial factor of their therapeutic efficacy, the currently marketed mRNA vaccines feature uniform substitution of uridine (U) by the corresponding C-nucleoside, pseudouridine (Ψ), in 1-N-methylated form. Synthetic supply of the mRNA building block (1-N-Me-Ψ-5'-triphosphate) involves expedient access to Ψ as the principal challenge. Here, we show selective and atom-economic 1N-5C rearrangement of β-D-ribosyl on uracil to obtain Ψ from unprotected U in quantitative yield. One-pot cascade transformation of U in four enzyme-catalyzed steps, via D-ribose (Rib)-1-phosphate, Rib-5-phosphate (Rib5P) and Ψ-5'-phosphate (ΨMP), gives Ψ. Coordinated function of the coupled enzymes in the overall rearrangement necessitates specific release of phosphate from the ΨMP, but not from the intermediary ribose phosphates. Discovery of Yjjg as ΨMP-specific phosphatase enables internally controlled regeneration of phosphate as catalytic reagent. With driving force provided from the net N-C rearrangement, the optimized U reaction yields a supersaturated product solution (∼250 g/L) from which the pure Ψ crystallizes (90% recovery). Scale up to 25 g isolated product at enzyme turnovers of ∼10
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