基于非天然结构组件的人工酶设计与应用

袁飞燕; 于洋; 李春

doi:10.12211/2096-8280.2020-008

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基于非天然结构组件的人工酶设计与应用

特约评述 | 更新时间：2025-12-24

- 基于非天然结构组件的人工酶设计与应用
- Artificial enzyme designs and its application based on non-natural structural elements
- 合成生物学 2020年1卷第6期页码：685-696
- 作者机构：
  
  北京理工大学化学与化工学院生化工程系，合成生物系统研究所，北京 100081
- 作者简介：
  
  [ "袁飞燕（1993—），女，博士研究生。研究方向为蛋白质设计与酶工程。E-mail：feiyanyuan@163.com" ]
  [ "于洋（1987—），男，博士，研究员、博士生导师。研究方向为蛋白质设计与酶工程。E-mail：yang_yu@outlook.com" ]
  [ "李春（1970—），男，博士，教授、博士生导师。研究方向为合成生物学。E-mail：lichun@bit.edu.cn" ]
- 基金信息：
  
  国家重点研发计划项目(2018YFA0903300;2016YFA0502400)
- DOI：10.12211/2096-8280.2020-008
  中图分类号： Q814.9
- 收稿：2020-02-09，
  
  修回：2020-04-30，
  
  纸质出版：2020-12-31
- 稿件说明：
移动端阅览
袁飞燕, 于洋, 李春. 基于非天然结构组件的人工酶设计与应用[J]. 合成生物学, 2020, 1(6): 685-696

YUAN Feiyan, YU Yang, LI Chun. Artificial enzyme designs and its application based on non-native structural elements[J]. Synthetic Biology Journal, 2020, 1(6): 685-696
袁飞燕, 于洋, 李春. 基于非天然结构组件的人工酶设计与应用[J]. 合成生物学, 2020, 1(6): 685-696 DOI： 10.12211/2096-8280.2020-008.

YUAN Feiyan, YU Yang, LI Chun. Artificial enzyme designs and its application based on non-native structural elements[J]. Synthetic Biology Journal, 2020, 1(6): 685-696 DOI： 10.12211/2096-8280.2020-008.

摘要

人工酶是由人类设计得到的具有类似天然酶活性的催化剂。人工酶设计可能成为天然酶研究的补充，揭示天然酶的催化机理，实现天然酶尚未实现的作用。酶由20种天然氨基酸残基以及有限种类的辅因子组成，限制了蛋白质可实现的结构、反应性和功能空间。通过在蛋白质中引入非天然结构组件，包括非天然氨基酸和非天然辅因子，可以得到具有较高催化活性或全新反应性的人工酶。本文总结了引入非天然氨基酸和非天然辅因子构建人工酶和高效制备此类人工酶的策略，并以参与氧化还原反应的人工金属酶为例，探讨构建人工酶的方法，包括通过基因密码子扩展技术引入含生物正交反应基团或金属螯合基团的非天然氨基酸，或通过非共价、共价相互作用在骨架蛋白中引入非天然金属卟啉和其他金属有机催化剂，展望了引入非天然结构组件结合计算设计或代谢工程构建人工酶的新方法，这有助于实现媲美天然酶效率的人工酶的设计与应用。

Abstract

Artificial enzymes are catalysts designed by humans beings with similar activities to those of natural enzymes. The design of artificial enzymes may be a supplement for the study of natural enzymes

which can reveal the catalytic mechanism of natural enzymes and lead to catalysts for novel reactions. Enzymes are composed of 20 kinds of natural amino acids residues and a limited number of cofactors

which limits the structure

reactivity and functional space that proteins can access. Artificial enzymes with high catalytic activity or novel reactivity can be obtained by introducing non-natural structural components

including unnatural amino acids and non-natural cofactors into proteins. This article summarizes strategies for construction of artificial enzymes and efficient preparations of such artificial enzymes with unnatural amino acids and non-natural cofactors. Taking artificial metalloenzymes involved in the redox reactions as examples

this review discusses methods to construct artificial enzymes through introduction of unnatural amino acids containing bio-orthogonal reaction groups or metal chelating groups by genetic codon expansion

or through introduction of non-natural metalloporphyrins and other organometallic catalysts into scaffold proteins by covalent or non-covalent attachments. Emerging methods for construction of artificial enzymes using non-natural structural elements combined with computational design or metabolic engineering is prospected. These will be helpful to accelerate the design and preparation of artificial enzymes

leading to artificial enzymes with comparable activities to the native enzymes

and they will have great potential for industrial applications.

关键词

Keywords

references

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