ArticleJournal of the American Chemical Society2016
Identification of Mechanism-Based Inactivation in P450-Catalyzed Cyclopropanation Facilitates Engineering of Improved Enzymes.
Article in Journal of the American Chemical Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Enzymatic Stereodivergent Synthesis of Azaspiro[2.y]alkanes.Journal of the American Chemical Society · 2025Article
- Noncanonical Amino Acids: Bringing New-to-Nature Functionalities to Biocatalysis.Chemical reviews · 2024Review
- Choose Your Own Adventure: A Comprehensive Database of Reactions Catalyzed by Cytochrome P450 BM3 Variants.ACS catalysis · 2024Review
- Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere.Chemical reviews · 2022Review
- New-to-nature chemistry from old protein machinery: carbene and nitrene transferases.Current opinion in biotechnology · 2021Review
- Navigating the Unnatural Reaction Space: Directed Evolution of Heme Proteins for Selective Carbene and Nitrene Transfer.Accounts of chemical research · 2021Review
- Nature's Machinery, Repurposed: Expanding the Repertoire of Iron-Dependent Oxygenases.ACS catalysis · 2020Article
- How Does Replacement of the Axial Histidine Ligand in CytochromeInternational journal of molecular sciences · 2020Article
- Broadening the scope of biocatalytic C-C bond formation.Nature reviews. Chemistry · 2020Article
- Stereoselective Bioreduction of α-diazo-β-keto Esters.Molecules (Basel, Switzerland) · 2020Article
- A de novo peroxidase is also a promiscuous yet stereoselective carbene transferase.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- A Continuing Career in Biocatalysis: Frances H. Arnold.ACS catalysis · 2019Article
- Site-Selective Functionalization of (spAngewandte Chemie (International ed. in English) · 2019Review
- Engineered CytochromeSynlett : accounts and rapid communications in synthetic organic chemistry · 2019Article
- Article
- Mechanisms of Cytochrome P450-Catalyzed Oxidations.ACS catalysis · 2018Article
- Formation and Cleavage of C-C Bonds by Enzymatic Oxidation-Reduction Reactions.Chemical reviews · 2018Review
- Carbene Transfer Reactions Catalysed by Dyes of the Metalloporphyrin Group.Molecules (Basel, Switzerland) · 2018Review
- Evolving artificial metalloenzymes via random mutagenesis.Nature chemistry · 2018Article
- Article
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7 authors.
Funding
Abstract
Following the recent discovery that heme proteins can catalyze the cyclopropanation of styrenyl olefins with high efficiency and selectivity, interest in developing new enzymes for a variety of non-natural carbene transfer reactions has burgeoned. The fact that diazo compounds and other carbene precursors are known mechanism-based inhibitors of P450s, however, led us to investigate if they also interfere with this new enzyme function. We present evidence for two inactivation pathways that are operative during cytochrome P450-catalyzed cyclopropanation. Using a combination of UV-vis, mass spectrometry, and proteomic analyses, we show that the heme cofactor and several nucleophilic side chains undergo covalent modification by ethyl diazoacetate (EDA). Substitution of two of the affected residues with less-nucleophilic amino acids led to a more than twofold improvement in cyclopropanation performance (total TTN). Elucidating the inactivation pathways of heme protein-based carbene transfer catalysts should aid in the optimization of this new biocatalytic function.
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