Identifying and Engineering Flavin Dependent Halogenases for Selective Biocatalysis,Accounts of Chemical Research

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Identifying and Engineering Flavin Dependent Halogenases for Selective Biocatalysis
Accounts of Chemical Research ( IF 16.4 ) Pub Date : 2024-07-22 , DOI: 10.1021/acs.accounts.4c00172
Jared C Lewis ₁

Affiliation

Organohalogen compounds are extensively used as building blocks, intermediates, pharmaceuticals, and agrochemicals due to their unique chemical and biological properties. Installing halogen substituents, however, frequently requires functionalized starting materials and multistep functional group interconversion. Several classes of halogenases evolved in nature to enable halogenation of a different classes of substrates; for example, site-selective halogenation of electron rich aromatic compounds is catalyzed by flavin-dependent halogenases (FDHs). Mechanistic studies have shown that these enzymes use FADH₂ to reduce O₂ to water with concomitant oxidation of X^– to HOX (X = Cl, Br, I). This species travels through a tunnel within the enzyme to access the FDH active site. Here, it is believed to interact with an active site lysine proximal to bound substrate, enabling electrophilic halogenation with selectivity imparted via molecular recognition, rather than directing groups or strong electronic activation.

中文翻译：

鉴定和改造用于选择性生物催化的黄素依赖性卤化酶

有机卤素化合物由于其独特的化学和生物特性而被广泛用作建筑材料、中间体、药物和农用化学品。然而，安装卤素取代基通常需要官能化的起始材料和多步官能团相互转化。自然界中进化出了几类卤化酶，能够卤化不同类的底物；例如，富电子芳香族化合物的位点选择性卤化是由黄素依赖性卤化酶（FDH）催化的。机理研究表明，这些酶利用 FADH ₂将 O ₂还原为水，同时将 X ^–氧化为 HOX (X = Cl、Br、I)。该物种通过酶内的隧道到达 FDH 活性位点。在这里，它被认为与接近结合底物的活性位点赖氨酸相互作用，从而通过分子识别赋予亲电卤化选择性，而不是引导基团或强电子激活。

更新日期：2024-07-22

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