ArticleACS catalysis2021
Unlocking Iminium Catalysis in Artificial Enzymes to Create a Friedel-Crafts Alkylase.
Article in ACS catalysis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Exploring PadR Proteins for Artificial Enzyme Design.Chembiochem : a European journal of chemical biology · 2026Article
- Engineering LmrR protein for L-proline-based asymmetric aldol biocatalysis.Nature communications · 2026Article
- Design and evolution of artificial enzyme with in-situ biosynthesized non-canonical amino acid.Nature communications · 2025Article
- Designing Enzymatic Reactivity with an Expanded Palette.Chembiochem : a European journal of chemical biology · 2025Review
- Iminium Catalysis in Natural Diels-Alderase.Nature catalysis · 2025Article
- Evolutionary Specialization of a Promiscuous Designer Enzyme.ACS catalysis · 2025Article
- Genetic Code Expansion: Recent Developments and Emerging Applications.Chemical reviews · 2025Review
- Boron Designer Enzyme with a Hybrid Catalytic Dyad.ACS catalysis · 2024Article
- Recent advances in the expanding genetic code.Current opinion in chemical biology · 2024Review
- Noncanonical Amino Acids: Bringing New-to-Nature Functionalities to Biocatalysis.Chemical reviews · 2024Review
- Noncanonical Amino Acids in Biocatalysis.Chemical reviews · 2024Review
- Genetically encoded Nδ-vinyl histidine for the evolution of enzyme catalytic center.Nature communications · 2024Article
- Review
- Secondary Amine Catalysis in Enzyme Design: Broadening Protein Template Diversity through Genetic Code Expansion.Angewandte Chemie (International ed. in English) · 2024Article
- Boron catalysis in a designer enzyme.Nature · 2024Article
- Rationally introducing non-canonical amino acids to enhance catalytic activity of LmrR for Henry reaction.Bioresources and bioprocessing · 2024Article
- Engineering enzyme activity using an expanded amino acid alphabet.Protein engineering, design & selection : PEDS · 2023Article
- In Vivo Biocatalytic Cascades Featuring an Artificial-Enzyme-Catalysed New-to-Nature Reaction.Angewandte Chemie (International ed. in English) · 2023Article
- Biocatalytic Friedel-Crafts Reactions.ChemCatChem · 2022Review
- Unlocking New Reactivities in Enzymes by Iminium Catalysis.Angewandte Chemie (International ed. in English) · 2022Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The construction and engineering of artificial enzymes consisting of abiological catalytic moieties incorporated into protein scaffolds is a promising strategy to realize non-natural mechanisms in biocatalysis. Here, we show that incorporation of the noncanonical amino acid para-aminophenylalanine (pAF) into the nonenzymatic protein scaffold LmrR creates a proficient and stereoselective artificial enzyme (LmrR_pAF) for the vinylogous Friedel-Crafts alkylation between α,β-unsaturated aldehydes and indoles. pAF acts as a catalytic residue, activating enal substrates toward conjugate addition via the formation of intermediate iminium ion species, while the protein scaffold provides rate acceleration and stereoinduction. Improved LmrR_pAF variants were identified by low-throughput directed evolution advised by alanine-scanning to obtain a triple mutant that provided higher yields and enantioselectivities for a range of aliphatic enals and substituted indoles. Analysis of Michaelis-Menten kinetics of LmrR_pAF and evolved mutants reveals that different activities emerge via evolutionary pathways that diverge from one another and specialize catalytic reactivity. Translating this iminium-based catalytic mechanism into an enzymatic context will enable many more biocatalytic transformations inspired by organocatalysis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.