ArticleNature catalysis2023
Mechanistic and structural characterization of an iridium-containing cytochrome reveals kinetically relevant cofactor dynamics.
Article in Nature catalysis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Asymmetric formal [1 + 2 + 2]-cycloaddition of diazoamides with enamines and carbonyl compounds.Nature communications · 2025Article
- Expanding the Terpene Universe: Synthetic Biology and Non-Natural Chemistry in Engineered Microorganisms.Molecules (Basel, Switzerland) · 2025Review
- Enantioselective Synthesis of Spirocyclic Nitrogen-Containing Heterocycles Catalyzed by an Iridium-Containing Cytochrome.Journal of the American Chemical Society · 2025Article
- Designing Enzymatic Reactivity with an Expanded Palette.Chembiochem : a European journal of chemical biology · 2025Review
- Kinetic Modeling Enables Understanding of Off-Cycle Processes in Pd-Catalyzed Amination of Five-Membered Heteroaryl Halides.Journal of the American Chemical Society · 2024Article
- Hybrid Metal Catalysts as Valuable Tools in Organic Synthesis: An Overview of the Recent Advances in Asymmetric C─C Bond Formation Reactions.Molecules (Basel, Switzerland) · 2024Review
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Authors and funding
9 authors.
Funding
Abstract
Artificial metalloenzymes (ArMs), which contain non-native, typically synthetic, metal cofactors, are a flourishing class of biocatalyst for unnatural reactions. Although the number of these reactions is rapidly increasing, multi-faceted mechanistic studies of ArMs comprising structural, kinetic, computational and cofactor binding data to reveal detailed mechanistic information on the effects of the protein scaffold on the structure and reactivity of ArMs are more limited. Here we report the structure of an unnatural P450 analogue using X-ray diffraction. We also report the kinetic analysis of its reaction, catalyst activation during an induction period, and the origins of the stereoselectivity for the cyclopropanation of a terpene catalysed by the iridium-containing P450 variant (Ir(Me)-CYP119). Our data reveal a mechanism initiated by the flip of the cofactor from an inactive to an active conformation. This change in conformation is followed by thousands of turnovers occurring by rate-determining formation of an iridium-carbene intermediate, thereby highlighting the influence of cofactor dynamics within a single active site on an ArM-catalysed reaction.
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Registered trials
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