Fe/
α- 酮戊二酸依赖型卤化酶在绿色卤化反应中的研究进展Recent advances of enzymatic synthesis of organohalogens catalyzed by Fe/
α KG-dependent halogenases- 合成生物学 2022年3卷第3期 页码：545-566
- 作者机构：
沈阳药科大学生命科学与生物制药学院，辽宁 沈阳 110016
- 作者简介：
[ "王汇滨（1998—），男，硕士研究生。研究方向为天然产物生物合成机制。 E-mail：huibin0918@163.com" ]
[ "游松（1963—），男，博士，教授，博士生导师。研究方向为生物催化与生物转化。 E-mail：yousong206@aliyun.com" ]
- 基金信息：国家重点研发计划“绿色生物制造”项目(2021YFC2102004)
DOI：10.12211/2096-8280.2021-102
中图分类号： Q554收稿：2021-11-10，
修回：2021-11-28，
纸质出版：2022-06-30
- 稿件说明：
移动端阅览
王汇滨， 车昌丽， 游松. Fe/α-酮戊二酸依赖型卤化酶在绿色卤化反应中的研究进展［J］. 合成生物学， 2022， 3（3）： 545-566
WANG Huibin， CHE Changli， YOU Song. Recent advances of enzymatic synthesis of organohalogens catalyzed by Fe/αKG-dependent halogenases［J］. Synthetic Biology Journal， 2022， 3（3）： 545-566
王汇滨， 车昌丽， 游松. Fe/α-酮戊二酸依赖型卤化酶在绿色卤化反应中的研究进展［J］. 合成生物学， 2022， 3（3）： 545-566 DOI： 10.12211/2096-8280.2021-102.
WANG Huibin， CHE Changli， YOU Song. Recent advances of enzymatic synthesis of organohalogens catalyzed by Fe/αKG-dependent halogenases［J］. Synthetic Biology Journal， 2022， 3（3）： 545-566 DOI： 10.12211/2096-8280.2021-102.
摘要
将卤素原子引入药物、农药等小分子中可以有效提升其生物活性，并且碳卤键可用于有机合成后期功能化反应。Fe/
α
-酮戊二酸（
α
-ketoglutaric acid，
α
KG）依赖型卤化酶可以高立体选择性和区域选择性催化卤素原子引入到未经活化的sp
3
杂化碳中心。大自然是最伟大的化学家，本文遵循从学习自然到改造自然的逻辑顺序，首先介绍Fe
/
α
KG依赖型卤化酶的发现历程，之后分别总结天然产物生物合成途径中的载体依赖型和独立型Fe/
α
KG依赖型卤化酶，进一步分析Fe/
α
KG依赖型卤化酶的结构特征以及基于蛋白质工程等方法改造扩展其底物谱并拓展新的反应类型，最后从新酶的挖掘与表征、酶催化活性的提升、酶区域选择性的控制、酶反应类型的拓展、人工生物合成途径的创建等5方面进行展望，丰富对Fe/
α
KG依赖型卤化酶的催化机制、底物范围和反应杂泛性的相关认识，为后续合成生物学的应用研究奠定酶学基础。
Abstract
Synthetic biology is being developed as a bio-design and production platform through which more and more impressive products are synthesized. Enzymes
the cornerstone of synthetic biology
can catalyze diverse reactions
such as the concise synthesis of chiral alcohols and chiral amines. The biocatalytic halogenation reaction has gained research interest in recent years due to its mild reaction conditions and high selectivity. The insertion of halogen atoms into reaction agents such as drugs and agrochemicals can effectively enhance their biological activities
and the carbon-halogen bonds can be employed as a key building block for the late-stage functionalization reactions. Fe/
α
-ketoglutaric acid (
α
KG)-dependent halogenases can catalyze the insertion of halogen atoms into unactivated sp
3
-hybridized carbon centers with high stereoselectivity and regioselectivity based on the radical reaction mechanism. This review follows the logical sequence of learning from the nature
a powerful chemist. First
it introduces the discovery of Fe/
α
KG-dependent halogenases
and then summarizes the carrier protein-dependent and non-dependent Fe/
α
KG-dependent halogenases involved in the biosynthesis of natural products. Furthermore
it analyzes the structural characteristics of Fe/
α
KG-dependent halogenases
and address their substrate spectrum and novel reaction types expanded and created through protein engineering and other methods. Finally
the discovery and characterization of new enzymes
the improvement of their catalytic activities
the rational control of their regios
electivities
the expansion of tehir reaction types
and the creation of the artificial biosynthetic pathways are highlighted
expecting to enrich the knowledge on the catalytic mechanism
substrate scope and reaction promiscuity of Fe/
α
KG-dependent halogenases. Learning the cryptic chemistry mechanism hidden with natural products remains one of the hot topics in natural product chemistry. Beyond that
rational redesign and evolution of “supra-natural” product pathways will be emphasized for the purpose of discovering and developing novel lead compounds from an interdisciplinary point of view under the guidance of the synthetic biology. The review would lay a enzymology foundation for the related and subsequent research in synthetic biology.
2
关键词
Keywords
references
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