Huang Yujia, Zhang Pan, Wang Haoyu, Chen Yan, Liu Tao, Luo Xiaozhou
State Key Laboratory of Natural and Biomimetic Drugs, Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Chemical Biology Center, Peking University, Beijing 100191, China.
Shenzhen Key Laboratory for the Intelligent Microbial Manufacturing of Medicines, Key Laboratory of Quantitative Synthetic Biology, Center for Synthetic Biochemistry, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, P.R. China.
Chem Rev. 2025 Jan 22;125(2):523-598. doi: 10.1021/acs.chemrev.4c00216. Epub 2024 Dec 31.
The concept of genetic code expansion (GCE) has revolutionized the field of chemical and synthetic biology, enabling the site-specific incorporation of noncanonical amino acids (ncAAs) into proteins, thus opening new avenues in research and applications across biology and medicine. In this review, we cover the principles of GCE, including the optimization of the aminoacyl-tRNA synthetase (aaRS)/tRNA system and the advancements in translation system engineering. Notable developments include the refinement of aaRS/tRNA pairs, enhancements in screening methods, and the biosynthesis of noncanonical amino acids. The applications of GCE technology span from synthetic biology, where it facilitates gene expression regulation and protein engineering, to medicine, with promising approaches in drug development, vaccine production, and gene editing. The review concludes with a perspective on the future of GCE, underscoring its potential to further expand the toolkit of biology and medicine. Through this comprehensive review, we aim to provide a detailed overview of the current state of GCE technology, its challenges, opportunities, and the frontier it represents in the expansion of the genetic code for novel biological research and therapeutic applications.
遗传密码扩展（GCE）的概念彻底改变了化学和合成生物学领域，使非天然氨基酸（ncAAs）能够位点特异性地掺入蛋白质中，从而为生物学和医学的研究与应用开辟了新途径。在本综述中，我们涵盖了GCE的原理，包括氨酰-tRNA合成酶（aaRS）/tRNA系统的优化以及翻译系统工程的进展。显著的进展包括aaRS/tRNA对的优化、筛选方法的改进以及非天然氨基酸的生物合成。GCE技术的应用范围广泛，从合成生物学（促进基因表达调控和蛋白质工程）到医学（在药物开发、疫苗生产和基因编辑方面有前景的方法）。综述最后展望了GCE的未来，强调其进一步扩展生物学和医学工具包的潜力。通过本全面综述，我们旨在详细概述GCE技术的现状、其挑战、机遇以及它在扩展遗传密码用于新型生物学研究和治疗应用方面所代表的前沿领域。
