基于吡咯赖氨酸正交翻译的基因密码子拓展技术的研究进展  

Advances in Genetic Codon Expansion of Pyrrolysine Orthogonal Translation

作　　者：邱泽凯 乔建军[1,2,3,4] 李艳妮 吴胜波[1,2] 朱宏吉[1,3] QIU Zekai;QIAO Jianjun;LI Yanni;WU Shengbo;ZHU Hongji(School of Chemical Engineering,Tianjin University,Tianjin 300072,China;Zhejiang Institute of Tianjin University(Shaoxing),Shaoxing 312300,China;Key Laboratory of Systems Bioengineering(Ministry of Education),Tianjin University,Tianjin 300072,China;Synthetic Biology Research Platform,Tianjin Collaborative Innovation Center of Chemical Science and Engineering,Tianjin 300072,China)

机构地区：[1]天津大学化工学院,天津300072 [2]天津大学浙江研究院(绍兴),绍兴312300 [3]系统生物工程教育部(天津大学)重点实验室,天津300072 [4]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》2024年第11期39-53,共15页China Biotechnology

基　　金：国家重点研发计划(2019YFA0904104)资助项目。

摘　　要：基因密码子拓展技术利用正交翻译系统,重新分配密码子并在目标蛋白质中位点特异地掺入非典型氨基酸。该技术拓展了蛋白质的结构和功能,在生物技术、医药研发等领域展示出极大潜力。吡咯赖氨酸正交翻译系统凭借独特的正交性与底物特异性成为目前应用广泛的密码子拓展工具。系统介绍了吡咯赖氨酸正交翻译系统的关键组成与优化方法,主要包括氨酰tRNA合成酶与tRNA的突变策略和非典型氨基酸供给优化策略。汇总了利用吡咯赖氨酰tRNA合成酶变体实现掺入的各类非典型氨基酸。接着,梳理了吡咯赖氨酸正交翻译系统在蛋白质翻译调控、生物医药研发和编码非L-α-氨基酸等领域的前沿进展。最后,探讨了吡咯赖氨酸正交翻译系统当下面临的机遇与挑战。Genetic codon expansion technology utilizes orthogonal translation systems to achieve site-specific incorporation of non-canonical amino acids into target proteins by reprogramming codons.This technology extends the structure and function of proteins and has great potential in biotechnology,pharmaceutical research and other fields.The pyrrolysine orthogonal translation system has become a widely used codon expansion tool due to its unique orthogonality and substrate specificity.This article begins with an introduction to the key components and optimization methods of the pyrrolysine orthogonal translation system,including aminoacyl-tRNA synthetase and tRNA mutation strategies and non-canonical amino acid supply optimization strategies.Furthermore,various types of non-canonical amino acids incorporated by pyrrolysyl-tRNA synthetase variants are assembled and condensed.Next,the frontier progress of the pyrrolysine orthogonal translation system in protein function regulation,biomedical research,and non-L-α-amino acid coding is summarized to provide an overview.Finally,the current opportunities and challenges for the development of the pyrrolysine orthogonal translation system are explored.

关 键 词：基因密码子拓展 吡咯赖氨酰tRNA合成酶 正交翻译 非L-α-氨基酸 

分 类 号：Q812[生物学—生物工程]