Mechanistic Investigation of a Non-Heme Iron Enzyme Catalyzed Epoxidation in (−)-4′-Methoxycyclopenin Biosynthesis

Chang, Wei‐chen; Li, Jikun; Lee, Justin L.; Cronican, Andrea A.; Guo, Yisong

doi:10.1021/jacs.6b05400

Cited by 51 publications

(50 citation statements)

References 42 publications

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“…When 5‐ 2 H 2 ‐ 1 was used, the sample quenched at 0.03 seconds and showed about a 30 % decrease of the SfaA⋅Fe II ⋅2OG⋅5‐ 2 H 2 ‐ 1 complex with simultaneous accumulation of a species with parameters of δ =0.31 mm s −1 and Δ E Q =0.59 mm s −1 , representing about 20 % of the total iron. This new species is similar to the ferryl intermediate observed in other Fe/2OG enzymes . In addition, a minor ferrous species with parameters of δ =1.25 mm s −1 and Δ E Q =1.90 mm s −1 (≈13 % of the iron in the sample) was also observed.…”

Section: Methodsmentioning

confidence: 99%

Pathway from N‐Alkylglycine to Alkylisonitrile Catalyzed by Iron(II) and 2‐Oxoglutarate‐Dependent Oxygenases

Chen

Tang

et al. 2020

Angew Chem Int Ed

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N‐alkylisonitrile, a precursor to isonitrile‐containing lipopeptides, is biosynthesized by decarboxylation‐assisted ‐N≡C group (isonitrile) formation by using N‐alkylglycine as the substrate. This reaction is catalyzed by iron(II) and 2‐oxoglutarate (Fe/2OG) dependent enzymes. Distinct from typical oxygenation or halogenation reactions catalyzed by this class of enzymes, installation of the isonitrile group represents a novel reaction type for Fe/2OG enzymes that involves a four‐electron oxidative process. Reported here is a plausible mechanism of three Fe/2OG enzymes, Sav607, ScoE and SfaA, which catalyze isonitrile formation. The X‐ray structures of iron‐loaded ScoE in complex with its substrate and the intermediate, along with biochemical and biophysical data reveal that ‐N≡C bond formation involves two cycles of Fe/2OG enzyme catalysis. The reaction starts with an FeIV‐oxo‐catalyzed hydroxylation. It is likely followed by decarboxylation‐assisted desaturation to complete isonitrile installation.

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Section: Methodsmentioning

confidence: 99%

Pathway from N‐Alkylglycine to Alkylisonitrile Catalyzed by Iron(II) and 2‐Oxoglutarate‐Dependent Oxygenases

Chen

Tang

et al. 2020

Angew Chem Int Ed

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“…Namely, during the second reaction, the presumptive ferryl species is used to trigger decarboxylation by activating N, and the reaction is then followed by dehydration (3!8!2). Alternatively, subsequent to dehydration of 3, an analogous decarboxylation will result in protonated isonitrile (9). Although it is less common, desaturation by oxidative decarboxylation has been reported in several Fe/2OG enzyme catalyzed olefination.…”

Section: Angewandte Chemiementioning

confidence: 99%

Pathway from N‐Alkylglycine to Alkylisonitrile Catalyzed by Iron(II) and 2‐Oxoglutarate‐Dependent Oxygenases

Chen

Tang

et al. 2020

Angewandte Chemie

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N-alkylisonitrile, a precursor to isonitrile-containing lipopeptides, is biosynthesized by decarboxylation-assisted -NC group (isonitrile) formation by using N-alkylglycine as the substrate. This reaction is catalyzed by iron(II) and 2oxoglutarate (Fe/2OG) dependent enzymes. Distinct from typical oxygenation or halogenation reactions catalyzed by this class of enzymes, installation of the isonitrile group represents a novel reaction type for Fe/2OG enzymes that involves a four-electron oxidative process. Reported here is a plausible mechanism of three Fe/2OG enzymes, Sav607, ScoE and SfaA, which catalyze isonitrile formation. The X-ray structures of iron-loaded ScoE in complex with its substrate and the intermediate, along with biochemical and biophysical data reveal that -NC bond formation involves two cycles of Fe/2OG enzyme catalysis. The reaction starts with an Fe IV -oxocatalyzed hydroxylation. It is likely followed by decarboxylation-assisted desaturation to complete isonitrile installation.

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“…FQ Mössbauer analysis has been used to detect similar Fe(IV) intermediate species in several other family representatives (e.g. [27–29, 58, 59]).…”

Section: Mössbauer and Xas Analysis Of Taudmentioning

confidence: 99%

Spectroscopic analyses of 2-oxoglutarate-dependent oxygenases: TauD as a case study

2016

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A wide range of spectroscopic approaches have been used to interrogate the mononuclear iron metallocenter in 2-oxoglutarate (2OG)-dependent oxygenases. The results from these spectroscopic studies have provided valuable insights into the structural changes at the active site during substrate binding and catalysis, thus providing critical information that complements investigations of these enzymes by x-ray crystallography, biochemical, and computational approaches. This mini-review highlights taurine hydroxylase (taurine:2OG dioxygenase, TauD) as a case study to illustrate the wealth of knowledge that can be generated by applying a diverse array of spectroscopic investigations to a single enzyme. In particular, electronic absorption, circular dichroism, magnetic circular dichroism, conventional and pulse electron paramagnetic, Mössbauer, X-ray absorption, and resonance Raman methods have been exploited to uncover the properties of the metal site in TauD.

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Mechanistic Investigation of a Non-Heme Iron Enzyme Catalyzed Epoxidation in (−)-4′-Methoxycyclopenin Biosynthesis

Cited by 51 publications

References 42 publications

Pathway from N‐Alkylglycine to Alkylisonitrile Catalyzed by Iron(II) and 2‐Oxoglutarate‐Dependent Oxygenases

Pathway from N‐Alkylglycine to Alkylisonitrile Catalyzed by Iron(II) and 2‐Oxoglutarate‐Dependent Oxygenases

Pathway from N‐Alkylglycine to Alkylisonitrile Catalyzed by Iron(II) and 2‐Oxoglutarate‐Dependent Oxygenases

Spectroscopic analyses of 2-oxoglutarate-dependent oxygenases: TauD as a case study

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