ArticleNature2025
Emergence of a distinct mechanism of C-N bond formation in photoenzymes.
Article in Nature, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Machine-Learning-Enabled Rapid Evolution of Photoenzymes for the Asymmetric Synthesis of gem-Difluorophosphonates.Angewandte Chemie (International ed. in English) · 2026Article
- Directed evolution of an enantiocomplementary SNature communications · 2026Article
- Nitrene generation and transfer for unnatural biosynthesis in living cells.Nature chemistry · 2026Article
- Catalytic Enantioselective Intramolecular Aza-Michael Addition to α,β-Unsaturated Esters.Angewandte Chemie (International ed. in English) · 2026Article
- Asymmetric Hydroamination Using Oxidative Radical Initiation in Flavin Enzymes.Journal of the American Chemical Society · 2026Article
- A programmable bifunctional flavoenzyme for direct amine-to-ester conversion.Science advances · 2026Article
- Photochemical, electrochemical and electrophotochemical C-N bond-forming cross-coupling reactions.Nature reviews. Chemistry · 2026Review
- First Access to Tetraazadiindenopyrenes via Selective Pyrrole Cyclization of Phenyl-Substituted Tetraazapyrene Derivatives on Au(111).Small science · 2026Article
- Establishing the Fatty Acid PhotodecarboxylaseACS catalysis · 2026Article
- Assembling a single active pocket from enzyme and metal modules for simultaneously catalyzing oxidation-reduction cascades.Nature communications · 2026Article
- Biocatalytic Radical C(spResearch square · 2026Article
- Azetidine amino acid biosynthesis by non-haem iron-dependent enzymes.Nature chemistry · 2026Article
- Stereoconvergent Photo-Biocatalytic Cascade to Optically Enriched Amines from Racemic Carboxylic Acids.ACS omega · 2026Article
- Designing and Engineering Enzymes for New-to-Nature Photobiocatalysis.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Protein-confined imidazolium intermediates enable diverse biocatalytic C-C and C-N bond formations.Nature catalysis · 2026Article
- Stereoselective Photoenzymatic Hydroarylation for the Construction of Quaternary Stereocenters.Journal of the American Chemical Society · 2025Article
- Aromatic Coupling Reactions Catalyzed by "ene"-Reductase under Visible Light Irradiation.ACS omega · 2025Article
- Enantioconvergent benzylic C(spScience (New York, N.Y.) · 2025Article
- Emergent Mechanisms in Biocatalysis.ACS central science · 2025Review
- Cooperative Photometallobiocatalysis: Nonheme Fe Enzyme-Catalyzed Enantioconvergent Radical Decarboxylative Azidation, Thiocyanation, and Isocyanation of Redox-Active Esters.Angewandte Chemie (International ed. in English) · 2025Article
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Authors and funding
4 authors.
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Abstract
C-N bond formation is integral to modern chemical synthesis owing to the ubiquity of nitrogen heterocycles in small-molecule pharmaceuticals and agrochemicals. Alkene hydroamination with unactivated alkenes is an atom-economical strategy for constructing these bonds. However, these reactions are challenging to render asymmetric when preparing fully substituted carbon stereocentres. Here we report a photoenzymatic alkene hydroamination to prepare 2,2-disubstituted pyrrolidines by a Baeyer-Villiger mono-oxygenase. Five rounds of protein engineering afforded a mutant, providing excellent product yield and stereoselectivity. Unlike related photochemical hydroaminations, which rely on the oxidation of the amine or alkene for C-N bond formation, this work exploits a through-space interaction of a reductively generated benzylic radical and the nitrogen lone pair. This antibonding interaction lowers the oxidation potential of the radical, enabling electron transfer to the flavin cofactor. Experiments indicate that the enzyme microenvironment is essential in enabling a innovative C-N bond formation mechanism with no parallel in small-molecule catalysis. Molecular dynamics simulations were performed to investigate the substrate in the enzyme active site, which further support this hypothesis. This work is a rare example of an emerging mechanism in non-natural biocatalysis in which an enzyme has access to a mechanism that its individual components do not. Our study showcases the potential of enhancing emergent mechanisms using protein engineering to provide unique mechanistic solutions to unanswered challenges in chemical synthesis.
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