Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, Otfried-Müller-Strasse 25, 72076, Tübingen, Germany.
Chembiochem. 2020 Nov 16;21(22):3169-3179. doi: 10.1002/cbic.202000300. Epub 2020 Jul 20.
Genetic code expansion is one of the most powerful technologies in protein engineering. In addition to the 20 canonical amino acids, the expanded genetic code is supplemented by unnatural amino acids, which have artificial side chains that can be introduced into target proteins in vitro and in vivo. A wide range of chemical groups have been incorporated co-translationally into proteins in single cells and multicellular organisms by using genetic code expansion. Incorporated unnatural amino acids have been used for novel structure-function relationship studies, bioorthogonal labelling of proteins in cellulo for microscopy and in vivo for tissue-specific proteomics, the introduction of post-translational modifications and optical control of protein function, to name a few examples. In this Minireview, the development of genetic code expansion technology is briefly introduced, then its applications in neurobiology are discussed, with a focus on studies using mammalian cells and mice as model organisms.
遗传密码扩展是蛋白质工程中最强大的技术之一。除了 20 种标准氨基酸外，扩展的遗传密码还补充了非天然氨基酸，这些氨基酸具有人工侧链，可以在体外和体内引入目标蛋白质。通过遗传密码扩展，广泛的化学基团已经被共翻译地整合到单细胞和多细胞生物的蛋白质中。通过遗传密码扩展，已经将非天然氨基酸整合到蛋白质中，用于研究新的结构-功能关系、细胞内蛋白质的生物正交标记用于显微镜和体内组织特异性蛋白质组学、翻译后修饰的引入和蛋白质功能的光控，仅举几例。在这篇综述中，简要介绍了遗传密码扩展技术的发展，然后讨论了其在神经生物学中的应用，重点是使用哺乳动物细胞和小鼠作为模式生物的研究。
