Mechanism of oxidative ring-closure as part of the hygromycin biosynthesis step by a nonheme iron dioxygenaseCitation formats

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Mechanism of oxidative ring-closure as part of the hygromycin biosynthesis step by a nonheme iron dioxygenase. / Ali, Hafiz Saqib; Henchman, Richard; De Visser, Samuel.

In: ChemCatChem, 11.04.2021.

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@article{5443c09942c04fe888228f92133dc966,
title = "Mechanism of oxidative ring-closure as part of the hygromycin biosynthesis step by a nonheme iron dioxygenase",
abstract = "Nonheme iron dioxygenases catalyze vital reactions for biosystems including the biosynthesis of antibiotics. One such enzyme, namely hygromycin (HygX), performs an oxidative ring-closure reaction to form an ortho-ester product, which is a relevant reaction step in drug synthesis and biotechnology. To understand the selective reaction mechanism of oxidative ring-closure to form ortho-ester products, we investigated the catalytic reaction mechanism of HygX leading to various products. Large active site cluster models were set-up and various pathways for substrate activation have been calculated. The work identifies a high-valent iron(IV)-oxo species in the quintet spin state as the active oxidant that selectively abstracts a proton of an alcohol group of the substrate, which is followed by a hydrogen atom abstraction from a tertiary CH group and rapid electron transfer. The latter formed biradical intermediate rearranges to form the desaturated ring-closed product. The calculations show that an active site Lys residue donates positive charge to the metal-oxo group and guides the reaction to a chemoselective desaturation pathway.",
author = "Ali, {Hafiz Saqib} and Richard Henchman and {De Visser}, Samuel",
year = "2021",
month = apr,
day = "11",
language = "English",
journal = "ChemCatChem",
issn = "1867-3880",
publisher = "John Wiley & Sons Ltd",

}

RIS

TY - JOUR

T1 - Mechanism of oxidative ring-closure as part of the hygromycin biosynthesis step by a nonheme iron dioxygenase

AU - Ali, Hafiz Saqib

AU - Henchman, Richard

AU - De Visser, Samuel

PY - 2021/4/11

Y1 - 2021/4/11

N2 - Nonheme iron dioxygenases catalyze vital reactions for biosystems including the biosynthesis of antibiotics. One such enzyme, namely hygromycin (HygX), performs an oxidative ring-closure reaction to form an ortho-ester product, which is a relevant reaction step in drug synthesis and biotechnology. To understand the selective reaction mechanism of oxidative ring-closure to form ortho-ester products, we investigated the catalytic reaction mechanism of HygX leading to various products. Large active site cluster models were set-up and various pathways for substrate activation have been calculated. The work identifies a high-valent iron(IV)-oxo species in the quintet spin state as the active oxidant that selectively abstracts a proton of an alcohol group of the substrate, which is followed by a hydrogen atom abstraction from a tertiary CH group and rapid electron transfer. The latter formed biradical intermediate rearranges to form the desaturated ring-closed product. The calculations show that an active site Lys residue donates positive charge to the metal-oxo group and guides the reaction to a chemoselective desaturation pathway.

AB - Nonheme iron dioxygenases catalyze vital reactions for biosystems including the biosynthesis of antibiotics. One such enzyme, namely hygromycin (HygX), performs an oxidative ring-closure reaction to form an ortho-ester product, which is a relevant reaction step in drug synthesis and biotechnology. To understand the selective reaction mechanism of oxidative ring-closure to form ortho-ester products, we investigated the catalytic reaction mechanism of HygX leading to various products. Large active site cluster models were set-up and various pathways for substrate activation have been calculated. The work identifies a high-valent iron(IV)-oxo species in the quintet spin state as the active oxidant that selectively abstracts a proton of an alcohol group of the substrate, which is followed by a hydrogen atom abstraction from a tertiary CH group and rapid electron transfer. The latter formed biradical intermediate rearranges to form the desaturated ring-closed product. The calculations show that an active site Lys residue donates positive charge to the metal-oxo group and guides the reaction to a chemoselective desaturation pathway.

M3 - Article

JO - ChemCatChem

JF - ChemCatChem

SN - 1867-3880

ER -