ArticleNature chemistry2015
Enzymatic hydroxylation of an unactivated methylene C-H bond guided by molecular dynamics simulations.
Article in Nature chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Article
- Characterization of the ketoreductase domain of pikromycin module 2.Chemical science · 2026Article
- Divergent evolution of fungal P450 monooxygenase unlocks simultaneous access to C12β and C15α oxyfunctionalization of steroids.Nature communications · 2025Article
- Biosynthesis of the 5-Isoxazolidinone-Containing Hexacyclic Structure of Parnafungin.Journal of the American Chemical Society · 2025Article
- Chemoenzymatic Skeletal Editing of Natural Product Scaffolds via P450-Controlled Site-Selective Ring Expansion at Aliphatic C─H Sites.Angewandte Chemie (International ed. in English) · 2025Article
- The Role of the Unusual 2-Tyr-1-carboxylate Non-heme Iron Motif in the Mechanism of N,N-Dimethylformamidase.ACS catalysis · 2025Article
- Shaping of a Reactive Manganese Catalyst Enables Access to Polyfunctionalized Cyclohexanes via Enantioselective C(spAngewandte Chemie (International ed. in English) · 2025Article
- SubTuner leverages physics-based modeling to complement AI in enzyme engineering toward non-native substrates.Chem catalysis · 2025Article
- Three distinct strategies lead to programmable aliphatic C-H oxidation in bicyclomycin biosynthesis.Nature communications · 2025Article
- Review
- Article
- Regioselective and enantioselective propargylic hydroxylations catalyzed by P450tol monooxygenases.Bioresources and bioprocessing · 2024Article
- Review
- EnzyHTP Computational Directed Evolution with Adaptive Resource Allocation.Journal of chemical information and modeling · 2023Article
- Highly Enantioselective Catalytic Lactonization at Nonactivated Primary and SecondaryJournal of the American Chemical Society · 2023Article
- C-H Bonds as Functional Groups: Simultaneous Generation of Multiple Stereocenters by Enantioselective Hydroxylation at Unactivated Tertiary C-H Bonds.Journal of the American Chemical Society · 2023Article
- Molecular Dynamics Simulations Guide Chimeragenesis and Engineered Control of Chemoselectivity in Diketopiperazine Dimerases.Angewandte Chemie (International ed. in English) · 2023Article
- Unnatural activities and mechanistic insights of cytochrome P450 PikC gained from site-specific mutagenesis by non-canonical amino acids.Nature communications · 2023Article
- Computation-Aided Engineering of Cytochrome P450 for the Production of Pravastatin.ACS catalysis · 2022Article
- Late-Stage Chemoenzymatic Installation of Hydroxy-Bearing Allyl Moiety on the Indole Ring of Tryptophan-Containing Peptides.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
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Authors and funding
14 authors.
Funding
Abstract
The hallmark of enzymes from secondary metabolic pathways is the pairing of powerful reactivity with exquisite site selectivity. The application of these biocatalytic tools in organic synthesis, however, remains under-utilized due to limitations in substrate scope and scalability. Here, we report how the reactivity of a monooxygenase (PikC) from the pikromycin pathway is modified through computationally guided protein and substrate engineering, and applied to the oxidation of unactivated methylene C-H bonds. Molecular dynamics and quantum mechanical calculations were used to develop a predictive model for substrate scope, site selectivity and stereoselectivity of PikC-mediated C-H oxidation. A suite of menthol derivatives was screened computationally and evaluated through in vitro reactions, where each substrate adhered to the predicted models for selectivity and conversion to product. This platform was also expanded beyond menthol-based substrates to the selective hydroxylation of a variety of substrate cores ranging from cyclic to fused bicyclic and bridged bicyclic compounds.
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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.