| 引用本文： |
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梁敏,黄媛林,罗月宁,杨登峰.Fe(Ⅱ)/α-酮戊二酸依赖型卤化酶作为生物催化剂的最新研究进展[J].广西科学院学报,2025,41(2):232-245. [点击复制]
- LIANG Min,HUANG Yuanlin,LUO Yuening,YANG Dengfeng.Recent Advances of Fe(Ⅱ)/α-ketoglutarate-dependent Halogenases as Biocatalysts[J].Journal of Guangxi Academy of Sciences,2025,41(2):232-245. [点击复制]
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| 摘要: |
| 生物催化碳氢键(C-H键)活化在药物和精细化学品合成中具有关键作用，而碳卤键(C-X键)的高选择性构建是其重要研究方向。尽管该领域已取得显著进展，但未活化的C(sp3)-H键的选择性卤化仍面临化学惰性突破、区域及立体控制等多重挑战。Fe(Ⅱ)/α-酮戊二酸(α-KG)依赖型卤化酶通过独特的自由基反应机制,能在温和条件下实现未活化的C(sp3)-H键中心碳的精准卤化，展现出优异的区域、化学和立体选择性，为药物合成提供创新工具。Fe(Ⅱ)/α-KG依赖型卤化酶包括载体蛋白型和独立型两类，其在生物碱、氨基酸和核苷酸等天然产物生物合成中的卤化反应备受关注。本文综述Fe(Ⅱ)/α-KG依赖型卤化酶的基本特性、催化机制和应用研究进展，并探讨利用基因挖掘等生物信息学方法发掘新型Fe(Ⅱ)/α-KG依赖型卤化酶的潜力，旨在为探索Fe(Ⅱ)/α-KG依赖型卤化酶作为生物催化剂在新型卤化物合成途径中的应用提供有价值的参考。 |
| 关键词: Fe(Ⅱ)/α-酮戊二酸依赖型卤化酶 生物催化剂 卤化反应 生物合成 |
| DOI：10.13657/j.cnki.gxkxyxb.20250722.009 |
| 投稿时间：2025-02-13修订日期：2025-03-11 |
| 基金项目:国家自然科学基金项目(32360244)，广西科技基地和人才专项(桂科AD23023007)，广西科学院基本科研业务费项目(2024YWF2114，CQ-C-202302)资助。 |
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| Recent Advances of Fe(Ⅱ)/α-ketoglutarate-dependent Halogenases as Biocatalysts |
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LIANG Min, HUANG Yuanlin, LUO Yuening, YANG Dengfeng
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| (Guangxi Key Laboratory of Marine Natural Products and Combinatorial Biosynthesis Chemistry, Guangxi Academy of Marine Sciences (Guangxi Mangrove Research Center), Guangxi Academy of Sciences, Nanning, Guangxi, 530007, China) |
| Abstract: |
| Carbon hydrogen bond (C-H bonds) activation by biocatalysis plays a key role in the synthesis of pharmaceuticals and fine chemicals, and the highly selective construction of carbon halogen bond (C-X bonds) is an important research direction. Although significant progress has been made in this field,the selective halogenation of unactivated C(sp3)-H bonds still faces multiple challenges such as chemical inertness breakthrough,regional and stereo-control. Fe(Ⅱ)/α-ketoglutarate (α-KG)-dependent halogenase can achieve precise halogenation of carbon centers in unactivated C(sp3)-H bonds under mild conditions through a unique free radical reaction mechanism, showing excellent regional,chemical and stereo-selectivity, providing an innovative tool for pharmaceutical synthesis. Fe(Ⅱ)/α-KG-dependent halogenases include carrier protein type and independent type, and their halogenation reactions in the biosynthesis of natural products such as alkaloids, amino acids and nucleotides have attracted much attention.In this paper,the basic characteristics,catalytic mechanism and application research progress of Fe(Ⅱ)/α-KG-dependent halogenases are reviewed.The potential of using bioinformatics methods such as gene mining to discover novel Fe(Ⅱ)/α-KG-dependent halogenases is also discussed.The aim is to provide a valuable reference for exploring the application of Fe(Ⅱ)/α-KG-dependent halogenase as a biocatalyst in the synthesis of novel halides. |
| Key words: Fe(Ⅱ)/α-ketoglutarate-dependent halogenase biocatalyst halogenation reaction biosynthesis |
