Tao Hui, Abe Ikuro
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo, Japan.
Eng Microbiol. 2022 Nov 29;3(1):100062. doi: 10.1016/j.engmic.2022.100062. eCollection 2023 Mar.
Fe(II)/α-ketoglutarate (αKG)-dependent oxygenases catalyze the oxidative modification of various molecules, from DNA, RNA, and proteins to primary and secondary metabolites. They also catalyze a variety of biochemical reactions, including hydroxylation, halogenation, desaturation, epoxidation, cyclization, peroxidation, epimerization, and rearrangement. Given the versatile catalytic capability of such oxygenases, numerous studies have been conducted to characterize their functions and elucidate their structure-function relationships over the past few decades. Amino acids, particularly nonproteinogenic amino acids, are considered as important building blocks for chemical synthesis and components for natural product biosynthesis. In addition, the Fe(II)/αKG-dependent oxygenase superfamily includes important enzymes for generating amino acid derivatives, as they efficiently modify various free-standing amino acids. The recent discovery of new Fe(II)/αKG-dependent oxygenases and the repurposing of known enzymes in this superfamily have promoted the generation of useful amino acid derivatives. Therefore, this study will focus on the recent progress achieved from 2019 to 2022 to provide a clear view of the mechanism by which these enzymes have expanded the repertoire of free amino acid oxidative modifications.
依赖Fe(II)/α-酮戊二酸（αKG）的加氧酶催化各种分子的氧化修饰，从DNA、RNA、蛋白质到初级和次级代谢产物。它们还催化多种生化反应，包括羟基化、卤化、去饱和、环氧化、环化、过氧化、差向异构化和重排。鉴于此类加氧酶具有多种催化能力，在过去几十年里，人们进行了大量研究来表征它们的功能并阐明其结构-功能关系。氨基酸，尤其是非蛋白质氨基酸，被视为化学合成的重要组成部分和天然产物生物合成的成分。此外，依赖Fe(II)/αKG的加氧酶超家族包括用于生成氨基酸衍生物的重要酶，因为它们能有效地修饰各种游离氨基酸。最近发现的新型依赖Fe(II)/αKG的加氧酶以及该超家族中已知酶的重新利用促进了有用氨基酸衍生物的生成。因此，本研究将聚焦于2019年至2022年取得的最新进展，以清晰了解这些酶扩展游离氨基酸氧化修饰种类的机制。
