Radical fluorine transfer catalysed by an engineered nonheme iron enzyme.

4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology
Methods in enzymology Pub Date : 2024-01-01 Epub Date: 2024-04-10 DOI:10.1016/bs.mie.2024.03.004
Qun Zhao, Zhenhong Chen, Jinyan Rui, Xiongyi Huang
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引用次数: 0

Abstract

Nonheme iron enzymes stand out as one of the most versatile biocatalysts for molecular functionalization. They facilitate a wide array of chemical transformations within biological processes, including hydroxylation, chlorination, epimerization, desaturation, cyclization, and more. Beyond their native biological functions, these enzymes possess substantial potential as powerful biocatalytic platforms for achieving abiological metal-catalyzed reactions, owing to their functional and structural diversity and high evolvability. To this end, our group has recently engineered a series of nonheme iron enzymes to employ non-natural radical-relay mechanisms for abiological radical transformations not previously known in biology. Notably, we have demonstrated that a nonheme iron enzyme, (S)-2-hydroxypropylphosphonate epoxidase from Streptomyces viridochromogenes (SvHppE), can be repurposed into an efficient and selective biocatalyst for radical fluorine transfer reactions. This marks the first known instance of a redox enzymatic process for C(sp3)F bond formation. This chapter outlines the detailed experimental protocol for engineering SvHPPE for fluorination reactions. Furthermore, the provided protocol could serve as a general guideline that might facilitate other engineering endeavors targeting nonheme iron enzymes for novel catalytic functions.

工程非血红素铁酶催化的自由基氟转移。
非血红素铁酶是用途最广泛的分子功能化生物催化剂之一。它们能促进生物过程中的一系列化学转化,包括羟化、氯化、外延化、去饱和、环化等。这些酶除了本身的生物功能外,由于其功能和结构的多样性以及高度的进化性,还具有作为强大生物催化平台的巨大潜力,可实现生物金属催化反应。为此,我们的研究小组最近设计了一系列非血红素铁酶,利用非天然自由基中继机制实现生物自由基转化,而这在以前的生物学中是不为人所知的。值得注意的是,我们已经证明,一种非血红素铁酶,即来自病毒变色链霉菌(SvHppE)的(S)-2-羟丙基膦酸环氧化物酶,可以被重新利用为一种高效、选择性的生物催化剂,用于自由基氟转移反应。这标志着首次已知的 C(sp3)F 键形成的氧化还原酶过程。本章概述了用于氟化反应的 SvHPPE 工程设计的详细实验方案。此外,所提供的实验方案还可以作为一个通用指南,促进其他针对非血红素铁酶的工程努力,以实现新的催化功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Methods in enzymology
Methods in enzymology 生物-生化研究方法
CiteScore
2.90
自引率
0.00%
发文量
308
审稿时长
3-6 weeks
期刊介绍: The critically acclaimed laboratory standard for almost 50 years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Each volume is eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Now with over 500 volumes the series contains much material still relevant today and is truly an essential publication for researchers in all fields of life sciences, including microbiology, biochemistry, cancer research and genetics-just to name a few. Five of the 2013 Nobel Laureates have edited or contributed to volumes of MIE.
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