Department of Chemistry , University of Pittsburgh , 219 Parkman Avenue , Pittsburgh , Pennsylvania 15237 , United States.
ACS Chem Biol. 2018 Sep 21;13(9):2375-2386. doi: 10.1021/acschembio.8b00520. Epub 2018 Sep 5.
Expanding the genetic code to enable the incorporation of unnatural amino acids into proteins in biological systems provides a powerful tool for studying protein structure and function. While this technology has been mostly developed and applied in bacterial and mammalian cells, it recently expanded into animals, including worms, fruit flies, zebrafish, and mice. In this review, we highlight recent advances toward the methodology development of genetic code expansion in animal model organisms. We further illustrate the applications, including proteomic labeling in fruit flies and mice and optical control of protein function in mice and zebrafish. We summarize the challenges of unnatural amino acid mutagenesis in animals and the promising directions toward broad application of this emerging technology.
扩展遗传密码以将非天然氨基酸掺入生物系统中的蛋白质中,为研究蛋白质结构和功能提供了强大的工具。尽管该技术主要在细菌和哺乳动物细胞中得到开发和应用,但最近已扩展到包括蠕虫、果蝇、斑马鱼和小鼠在内的动物中。在这篇综述中,我们重点介绍了在动物模型生物中扩展遗传密码的方法学发展的最新进展。我们进一步说明了该技术的应用,包括在果蝇和小鼠中的蛋白质组标记以及在小鼠和斑马鱼中对蛋白质功能的光学控制。我们总结了在动物中进行非天然氨基酸诱变的挑战以及朝着广泛应用这项新兴技术的有希望的方向。