基因密码子拓展技术的方法原理和前沿应用研究进展

付宪; 林涛; 张帆; 张惠铭; 章文蔚; 杨焕明; 朱师达; 徐讯; 沈玥

doi:10.12211/2096-8280.2020-007

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基因密码子拓展技术的方法原理和前沿应用研究进展

特约评述 | 更新时间：2025-03-20

- 基因密码子拓展技术的方法原理和前沿应用研究进展
- Progress in the study of genetic code expansion related methods, principles and applications
- 合成生物学 2020年1卷第1期页码：103-119
- 作者机构：
  
  1.深圳华大生命科学研究院,广东深圳518083
  2.广东省高通量基因组测序与合成编辑应用重点实验室，深圳华大生命科学研究院，广东深圳518120
  3.中国科学院大学华大教育中心，广东深圳518083
  4.（广东省）华大基因合成基因组学院士工作站, 深圳华大基因科技有限公司，广东深圳518120
  5.深圳创新分子诊断技术工程实验室，深圳华大生命科学研究院，广东深圳518120
  6.深圳国家基因库，广东深圳518120
- 作者简介：
  
  [ "付宪（1989-），男，博士，副研究员，研究方向为合成生物学、合成基因组学、蛋白质定向进化。E-mail:fuxian1@genomics.cn" ]
  [ "沈玥（1986-)，女，博士，研究员，研究方向为合成生物学、合成基因组学、DNA合成技术与工具开发。E-mail:shenyue@genomics.cn" ]
- 基金信息：
- DOI：10.12211/2096-8280.2020-007
  中图分类号： Q755
- 收稿：2020-02-28，
  
  修回：2020-03-25，
  
  纸质出版：2020-02-29
- 稿件说明：
移动端阅览
付宪, 林涛, 张帆, 张惠铭, 章文蔚, 杨焕明, 朱师达, 徐讯, 沈玥. 基因密码子拓展技术的方法原理和前沿应用研究进展[J]. 合成生物学, 2020, 1(1): 103-119

FU Xian, LIN Tao, ZHANG Fan, ZHANG Huiming, ZHANG Wenwei, YANG Huanming, ZHU Shida, XU Xun, SHEN Yue. Progress in the study of genetic code expansion related methods, principles and applications[J]. Synthetic Biology Journal, 2020, 1(1): 103-119
付宪, 林涛, 张帆, 张惠铭, 章文蔚, 杨焕明, 朱师达, 徐讯, 沈玥. 基因密码子拓展技术的方法原理和前沿应用研究进展[J]. 合成生物学, 2020, 1(1): 103-119 DOI： 10.12211/2096-8280.2020-007.

FU Xian, LIN Tao, ZHANG Fan, ZHANG Huiming, ZHANG Wenwei, YANG Huanming, ZHU Shida, XU Xun, SHEN Yue. Progress in the study of genetic code expansion related methods, principles and applications[J]. Synthetic Biology Journal, 2020, 1(1): 103-119 DOI： 10.12211/2096-8280.2020-007.

摘要

自然界生物根据其高度保守的密码子表来对20种天然氨基酸进行基因编码，这些种类有限的氨基酸构成了天然蛋白质合成的基本构筑单元。生物在漫长进化中通过改变蛋白质中氨基酸的排列顺序来丰富其结构与功能

但上述过程是随机的，缺乏可控性。拓展用于蛋白质合成的氨基酸种类亦可实现对蛋白质结构和功能的改变与操纵。通过对中心法则中翻译系统的设计与改造，基因密码子拓展技术可将非天然氨基酸特异性地引入到细胞内目标蛋白的指定位点，利用非天然氨基酸中特殊的官能团赋予目标蛋白新的物理化学性质，最终达到蛋白质功能创新的目的。本文主要介绍基因密码子拓展技术中翻译工具开发和适配底盘改造研究相关的原理、技术和前沿进展，讨论其在蛋白质功能调控、生物医药、生物防控等新兴领域应用中的成果进展与未来展望。

Abstract

All life on the earth uses a set of 20 amino acids to synthesize proteins according to the highly conservative codon table

and these limited kinds of amino acids serve as the building blocks for the natural protein synthesis. During the long-term evolution

nature is able to expand the structure and function of cellular proteins

via

changing the sequence order of amino acids. However

the evolution process is random and lack of controllability. Manipulating the structure and function of target proteins can also be realized by incorporating an expanded set of building blocks with new chemical and physical properties. Genetic code expansion for synthesis of proteins containing unnatural amino acids at any designed position can be achieved

via

the manipulation of the cellular components responsible for the translation step of the central dogma

which could endow target proteins with new and expanded properties. This review will be focused on the introduction of principles

strategies

techniques to engineer and rewire translational machinery and chassis underpinning genetic code expansion technology. Furthermore

emerging applications in the field of protein function regulation

innovative biomedicine and biocontainment relying on this technology will also be discussed.

Most lifes on the earth use a set of 20 naturally occurring amino acids as the building blocks for protein synthesis

according to the highly conserved codon table. Natural evolution modulates the structure and function of cellular proteins

via

random mutations among the limited

canonical collection of basic units. Instead

an expanded set of unnatural amino acids with new chemical and physic

al properties can be incorporated into proteins by synthetic biologists with molecular precision. Genetic code expansion for proteins can be achieved by engineering the translation step of the central dogma. This review will first introduce the principles

strategies

and techniques underpinning genetic code expansion technology

which targets the translational machinery in model chassis. Furthermore

emerging applications including protein function regulation

innovative biomedicine

and enhanced biocontainment will be discussed. We conclude with future perspectives.

关键词

Keywords

references

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