Artificial enzyme designs and its application based on non-natural structural elements

doi:10.12211/2096-8280.2020-008

Abstract

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.

Key words: artificial enzymes design, unnatural amino acid, non-natural cofactor, introduction strategy, redox reaction

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。

关键词: 人工酶设计, 非天然氨基酸, 非天然辅因子, 引入策略, 氧化还原反应

CLC Number:

Q814.9

Feiyan YUAN, Yang YU, Chun LI. Artificial enzyme designs and its application based on non-natural 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.

Figures/Tables 4

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