ArticleAngewandte Chemie (International ed. in English)2014
Improved cyclopropanation activity of histidine-ligated cytochrome P450 enables the enantioselective formal synthesis of levomilnacipran.
Article in Angewandte Chemie (International ed. in English), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 196 citations in OpenAlex.
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- Direct Access to Iron Carbenes from Aldehyde, Ketone, and Formamide Feedstocks.Journal of the American Chemical Society · 2026Article
- Computational design of generalist cyclopropanases with stereodivergent selectivity.Nature communications · 2026Article
- Mutations in active surface sites of NtGGPPS1 enhance carotenoid biosynthesis and drought resistance in Nicotiana tabacum.BMC plant biology · 2025Article
- Mechanistic investigation of sustainable heme-inspired biocatalytic synthesis of cyclopropanes for challenging substrates.Communications chemistry · 2024Article
- Choose Your Own Adventure: A Comprehensive Database of Reactions Catalyzed by Cytochrome P450 BM3 Variants.ACS catalysis · 2024Review
- Realizing the Continuous Chemoenzymatic Synthesis of Anilines Using an Immobilized Nitroreductase.ACS sustainable chemistry & engineering · 2023Article
- Construction of Biocatalysts Using the P450 Scaffold for the Synthesis of Indigo from Indole.International journal of molecular sciences · 2023Article
- Tryptophan-96 in cytochrome P450 BM3 plays a key role in enzyme survival.FEBS letters · 2023Article
- Synthese von α-Arylacrylamiden via Lewis Base vermitteltem Aryl/Wasserstoff-Austausch.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2022Article
- Synthesis of α-Aryl Acrylamides via Lewis-Base-Mediated Aryl/Hydrogen Exchange.Angewandte Chemie (International ed. in English) · 2022Article
- Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere.Chemical reviews · 2022Review
- Protein Engineering of an Artificial P450BM3 Peroxygenase System Enables Highly SelectiveMolecules (Basel, Switzerland) · 2022Article
- Extracellular Electron Transfer Enables Cellular Control of Cu(I)-Catalyzed Alkyne-Azide Cycloaddition.ACS central science · 2022Article
- Biocatalytic synthesis of non-standard amino acids by a decarboxylative aldol reaction.Nature catalysis · 2022Article
- Biocatalytic Asymmetric Cyclopropanations via Enzyme-Bound Iminium Ion Intermediates.Angewandte Chemie (International ed. in English) · 2021Article
- A Promiscuous Bacterial P450: The Unparalleled Diversity of BM3 in Pharmaceutical Metabolism.International journal of molecular sciences · 2021Review
- Directed Evolution. The Legacy of a Nobel Prize.Journal of molecular evolution · 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
2 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Engineering enzymes capable of modes of activation unprecedented in nature will increase the range of industrially important molecules that can be synthesized through biocatalysis. However, low activity for a new function is often a limitation in adopting enzymes for preparative-scale synthesis, reaction with demanding substrates, or when a natural substrate is also present. By mutating the proximal ligand and other key active-site residues of the cytochrome P450 enzyme from Bacillus megaterium (P450-BM3), a highly active His-ligated variant of P450-BM3 that can be employed for the enantioselective synthesis of the levomilnacipran core was engineered. This enzyme, BM3-Hstar, catalyzes the cyclopropanation of N,N-diethyl-2-phenylacrylamide with an estimated initial rate of over 1000 turnovers per minute and can be used under aerobic conditions. Cyclopropanation activity is highly dependent on the electronic properties of the P450 proximal ligand, which can be used to tune this non-natural enzyme activity.
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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.