基于古菌酪氨酰tRNA合成酶非天然氨基酸插入的研究进展  

Progress in Incorporation of Non-canonical Amino Acid Based on Archaeal Tyrosyl-tRNA Synthetase

作　　者：黄焕邦 吴洋[1,2,3] 杨友辉[1,2,3] 王兆官 齐浩 HUANG Huan-bang;WU Yang;YANG You-hui;WANG Zhao-guan;QI Hao(School of Chemical Engineering and Technology,Tianjin 300072,China;Key Laboratory of Systems Bioengineering of Ministry of Education,Tianjin 300072,China;Syn Bio Research Platform,Collaborative Innovation Center of Chemical Science and Engineering,Tianjin University,Tianjin 300072,China)

机构地区：[1]天津大学化工学院,天津300072 [2]系统生物工程教育部重点实验室,天津300072 [3]天津化学化工协同创新中心合成生物学平台,天津300072

出　　处：《中国生物工程杂志》2021年第9期110-125,共16页China Biotechnology

摘　　要：构筑蛋白质的编码信息存在于高度保守的密码子表中,而生物体仅利用20种天然氨基酸,就能排列组合出不同的蛋白质来行使多种生物学功能。通过合成生物学的飞速发展,使得在蛋白质合成中可控地引入非天然氨基酸成为可能。这极大地拓展了蛋白质的结构和功能,并为生物学工具的开发和生物生理过程的研究提供了便利。具有活性基团的非天然氨基酸可以广泛地应用于蛋白质结构研究、蛋白质功能调控以及新型生物材料构建和医药研发等诸多领域。基因密码子拓展技术利用正交翻译系统,通过重新分配密码子改造中心法则,可以在蛋白质的指定位点引入非天然氨基酸。系统地介绍了目前提升密码子拓展技术插入非天然氨基酸效率的方法,包括tRNA以及氨酰tRNA合成酶的各种突变方法和翻译辅助因子的改造。汇总了利用古细菌酪氨酰tRNA合成酶插入的非天然氨基酸和突变位点并总结了密码子拓展技术在生物医药领域的前沿进展。最后讨论了该项技术目前所面临的挑战,如可利用的密码子数量不多、正交翻译系统的种类有限和非天然氨基酸多插效率低下。希望能够帮助研究者建立适合的非天然氨基酸插入方法并推动密码子拓展技术进一步发展。The coding information used to build proteins exists in highly conserved codon table.In nature,organisms use 20 native amino acids to synthesize proteins of different lengths and orders to perform a variety of biological functions.In recent years,with the rapid development of synthetic biology,it is possible to controllably direct incorporation of non-canonical amino acids in protein synthesis.Non-canonical amino acids with functional side groups could extremely expand the structure and function of proteins,which could also be of benefit in the research of new synthetic biological tools and biological processes.The diversity of side chains serves in many fields,such as protein structure research,functional regulation,constructions of new bio-materials and biopharmaceutical industry development.This paper introduces the basic principle of the genetic codon expansion technology,and organizes the efficiency optimization strategies as well as new methods of constructing mutant library.In addition,it also summarizes the cutting-edge progress of the codon expansion technology in the field of bio-medicine.Finally,we summarize the current challenges faced by this technology,such as the limited number of available codons,the limited variety of orthogonal translation systems,and the low efficiency of multipleincorporation of unnatural amino acids.We hope that these contents could help researchers establish suitable methods for the insertion of unnatural amino acids and promote the further development of this technology.

关 键 词：密码子拓展 非天然氨基酸 生物正交 合成生物学 计算机辅助设计 

分 类 号：Q819[生物学—生物工程]