Biodegradation of Herbicides by a Plant Nonheme Iron Dioxygenase: Mechanism and Selectivity of Substrate Analogues

Lin, Yen-Ting; Ali, Hafiz Saqib; Visser, Sam P. de

doi:10.1002/chem.202103982

Cited by 7 publications

(2 citation statements)

References 105 publications

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“…A similar level of accuracy was obtained for the calculations of barrier heights of the oxygen atom transfer of biomimetic models, as compared to the experimental work (Cantú Reinhard et al, 2017;Mukherjee et al, 2019). Using cluster models, our groups also explored regioselectivities and pathways, leading to by-products (Timmins et al, 2017;Lin et al, 2022;Mokkawes and de Visser, 2023), and showed that these bifurcation pathways differ by only a few kcal mol −1 in some cases; hence, modeling will need to predict the correct ordering and able to deal with these small energy differences. The DFT calculations on large cluster models reproduce experimental product distributions very well, and hence, the systematic errors of the DFT approaches do not appear to influence the predictions of reaction mechanisms.…”

Section: Mechanism Of L-arginine Activation By Fe(ii)/αkg-dependent D...mentioning

confidence: 54%

Catalytic divergencies in the mechanism of L-arginine hydroxylating nonheme iron enzymes

Ali,

de Visser

2024

Front. Chem.

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Many enzymes in nature utilize a free arginine (L-Arg) amino acid to initiate the biosynthesis of natural products. Examples include nitric oxide synthases, which generate NO from L-Arg for blood pressure control, and various arginine hydroxylases involved in antibiotic biosynthesis. Among the groups of arginine hydroxylases, several enzymes utilize a nonheme iron(II) active site and let L-Arg react with dioxygen and α-ketoglutarate to perform either C3-hydroxylation, C4-hydroxylation, C5-hydroxylation, or C4−C5-desaturation. How these seemingly similar enzymes can react with high specificity and selectivity to form different products remains unknown. Over the past few years, our groups have investigated the mechanisms of L-Arg-activating nonheme iron dioxygenases, including the viomycin biosynthesis enzyme VioC, the naphthyridinomycin biosynthesis enzyme NapI, and the streptothricin biosynthesis enzyme OrfP, using computational approaches and applied molecular dynamics, quantum mechanics on cluster models, and quantum mechanics/molecular mechanics (QM/MM) approaches. These studies not only highlight the differences in substrate and oxidant binding and positioning but also emphasize on electronic and electrostatic differences in the substrate-binding pockets of the enzymes. In particular, due to charge differences in the active site structures, there are changes in the local electric field and electric dipole moment orientations that either strengthen or weaken specific substrate C−H bonds. The local field effects, therefore, influence and guide reaction selectivity and specificity and give the enzymes their unique reactivity patterns. Computational work using either QM/MM or density functional theory (DFT) on cluster models can provide valuable insights into catalytic reaction mechanisms and produce accurate and reliable data that can be used to engineer proteins and synthetic catalysts to perform novel reaction pathways.

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Section: Mechanism Of L-arginine Activation By Fe(ii)/αkg-dependent D...mentioning

confidence: 54%

Catalytic divergencies in the mechanism of L-arginine hydroxylating nonheme iron enzymes

Ali,

de Visser

2024

Front. Chem.

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“…AAD is expected to initially convert 2,4-D to its monohydroxylated product, and in a subsequent step, it is transformed into 2,4-DCP, which was characterized as the final product (Scheme ). , In this work, we constructed the reactant model of 2,4-D in complex with the AAD-1 and performed a series of QM/MM calculations to illuminate the chemistry of 2,4-D that occurred in the active site of AAD-1 (Scheme ).…”

Section: Introductionmentioning

confidence: 99%

Computational Study of the Fe(II) and α-Ketoglutarate-Dependent Aryloxyalkanoate Dioxygenase (AAD-1) in the Degradation of the Herbicide 2,4-Dichlorophenoxyacetic Acid

Zhang

Wang

Zhang

et al. 2023

J. Chem. Inf. Model.

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The AAD-1 enzyme belongs to the Fe(II) and αketoglutarate (Fe/αKG)-dependent nonheme aryloxyalkanoate dioxygenase family (AADs), which catalyzes the breakdown of 2,4-dichlorophenoxyacetic acid (2,4-D, an active ingredient of thousands of commercial herbicides) by using the highly active Fe(IV)�O complex. Multiple species of bacteria degrade 2,4-D via a pathway initiated by AADs; however, the detail of how they promote the cleavage of the ether C−O bond to generate 2,4dichlorophenol (2,4-DCP) and glyoxylate is still unclear, which is the prerequisite for the further degradation of these halogenated aromatics. In this work, based on the crystal structure of AAD-1, the computational models were constructed, and a series of QM/ MM and QM-only calculations were performed to explore the cleavage of the ether bond in 2,4-D with the catalysis of AAD-1. Our calculations reveal that AAD-1 may be only responsible for the hydroxylation of the substrate to generate the intermediate hemiacetal, which corresponds to an overall energy barrier of 14.2 kcal/mol on the quintet state surface, and the decomposition of the hemiacetal in the active site center of AAD-1 was calculated to be rather slow, corresponding to an energy barrier of 24.5 kcal/ mol. In contrast, the decomposition of the free hemiacetal molecule in a solvent was calculated to be quite easy. Whether the decomposition of the hemiacetal occurs inside or outside the activation site is still worthy of experimental verification.

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QM/MM Calculations Suggest Concerted O−O Bond Cleavage and Substrate Oxidation by Nonheme Diiron Toluene/o‐Xylene Monooxygenase

Zhou

Deng

et al. 2022

Chemistry An Asian Journal

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The nonheme diiron toluene/o-xylene monooxygenase (ToMO) is the most studied toluene monooxygenase that mediates an aromatic hydroxylation reaction. In this work, QM/MM calculations were performed to understand the reaction mechanism. It is revealed that the μ-η 2 :η 2 peroxodiferric species is the reactive intermediate after the binding of the O 2 molecule to the reduced diferrous center. Subsequently, both a stepwise and a concerted mechanism involving the critical OÀ O bond cleavage and CÀ O bond formation were considered. The latter was calculated to be more favorable, suggesting that the formation of a highvalent diferryl Q intermediate is not needed. The isomeric formation of the phenol product was found very facile. The first step was calculated to be rate-limiting, with a barrier of 17.6 kcal/mol for the ortho-hydroxylation.

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Biodegradation of Herbicides by a Plant Nonheme Iron Dioxygenase: Mechanism and Selectivity of Substrate Analogues

Cited by 7 publications

References 105 publications

Catalytic divergencies in the mechanism of L-arginine hydroxylating nonheme iron enzymes

Catalytic divergencies in the mechanism of L-arginine hydroxylating nonheme iron enzymes

Computational Study of the Fe(II) and α-Ketoglutarate-Dependent Aryloxyalkanoate Dioxygenase (AAD-1) in the Degradation of the Herbicide 2,4-Dichlorophenoxyacetic Acid

QM/MM Calculations Suggest Concerted O−O Bond Cleavage and Substrate Oxidation by Nonheme Diiron Toluene/o‐Xylene Monooxygenase

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