ArticleJournal of the American Chemical Society2016
Mechanism for Six-Electron Aryl-N-Oxygenation by the Non-Heme Diiron Enzyme CmlI.
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 20 papers.
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Who cites it
20 citing papers in PubMed.
- Heme oxygenase-like dimetal oxidases and oxygenases.Biochemical Society transactions · 2026Review
- The Heme Oxygenase-Like Diiron Enzyme HrmI Reveals Altered Regulatory Mechanisms for Dioxygen Activation and Substrate N-Oxygenation.Journal of the American Chemical Society · 2025Article
- Heme Oxygenase-Like Metalloenzymes.Annual review of biochemistry · 2025Review
- Nature of the Reactive Biferric Peroxy Intermediate P' in the Arylamine Oxygenases and Related Binuclear Fe Enzymes.Journal of the American Chemical Society · 2025Article
- Diverse N-Oxidation of Primary Aromatic Amines Controlled by Engineered P450 Peroxizyme Variants Facilitated by Dual-Functional Small Molecule.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Biocatalytic Strategies for Nitration Reactions.JACS Au · 2025Review
- Reconstitution of the Final Steps in the Biosynthesis of Valanimycin Reveals the Origin of Its Characteristic Azoxy Moiety.Angewandte Chemie (International ed. in English) · 2024Article
- Characterization of an efficient N-oxygenase from Saccharothrix sp. and its application in the synthesis of azomycin.Biotechnology for biofuels and bioproducts · 2023Article
- Article
- Mechanisms of OBiochemistry · 2021Article
- In Vitro Reconstitution Reveals a Central Role for the N-Oxygenase PvfB in (Dihydro)pyrazine-N-oxide and Valdiazen Biosynthesis.Angewandte Chemie (International ed. in English) · 2020Article
- The Diiron Monooxygenase CmlA from Chloramphenicol Biosynthesis Allows Reconstitution of β-Hydroxylation during Glycopeptide Antibiotic Biosynthesis.ACS chemical biology · 2019Article
- Diiron monooxygenases in natural product biosynthesis.Natural product reports · 2018Review
- Dioxygen Activation by Nonheme Diiron Enzymes: Diverse Dioxygen Adducts, High-Valent Intermediates, and Related Model Complexes.Chemical reviews · 2018Review
- CmlI N-Oxygenase Catalyzes the Final Three Steps in Chloramphenicol Biosynthesis without Dissociation of Intermediates.Biochemistry · 2017Article
- Unprecedented (μ-1,1-Peroxo)diferric Structure for the Ambiphilic Orange Peroxo Intermediate of the Nonheme N-Oxygenase CmlI.Journal of the American Chemical Society · 2017Article
- Time-Resolved Investigations of Heterobimetallic Cofactor Assembly in R2lox Reveal Distinct Mn/Fe Intermediates.Biochemistry · 2017Article
- Heteroatom-Heteroatom Bond Formation in Natural Product Biosynthesis.Chemical reviews · 2017Review
- Divergent mechanisms of iron-containing enzymes for hydrocarbon biosynthesis.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2017Review
- Activation of dioxygen by copper metalloproteins and insights from model complexes.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2017Review
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6 authors.
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Abstract
The ultimate step in chloramphenicol (CAM) biosynthesis is a six-electron oxidation of an aryl-amine precursor (NH2-CAM) to the aryl-nitro group of CAM catalyzed by the non-heme diiron cluster-containing oxygenase CmlI. Upon exposure of the diferrous cluster to O2, CmlI forms a long-lived peroxo intermediate, P, which reacts with NH2-CAM to form CAM. Since P is capable of at most a two-electron oxidation, the overall reaction must occur in several steps. It is unknown whether P is the oxidant in each step or whether another oxidizing species participates in the reaction. Mass spectrometry product analysis of reactions under (18)O2 show that both oxygen atoms in the nitro function of CAM derive from O2. However, when the single-turnover reaction between (18)O2-P and NH2-CAM is carried out in an (16)O2 atmosphere, CAM nitro groups contain both (18)O and (16)O, suggesting that P can be reformed during the reaction sequence. Such reformation would require reduction by a pathway intermediate, shown here to be NH(OH)-CAM. Accordingly, the aerobic reaction of NH(OH)-CAM with diferric CmlI yields P and then CAM without an external reductant. A catalytic cycle is proposed in which NH2-CAM reacts with P to form NH(OH)-CAM and diferric CmlI. Then the NH(OH)-CAM rereduces the enzyme diiron cluster, allowing P to reform upon O2 binding, while itself being oxidized to NO-CAM. Finally, the reformed P oxidizes NO-CAM to CAM with incorporation of a second O2-derived oxygen atom. The complete six-electron oxidation requires only two exogenous electrons and could occur in one active site.
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