The genetic code is the manual that cells use to incorporate amino acids into proteins. It is possible to artificially expand this manual through cellular, molecular, and chemical manipulations to improve protein functionality. Strategies for in vivo genetic code expansion are under the same functional constraints as natural protein synthesis. Here, we review the approaches used to incorporate noncanonical amino acids (ncAAs) into designer proteins through the manipulation of the translation machinery and draw parallels between these methods and natural adaptations that improve translation in extant organisms. Following this logic, we propose new nature-inspired tactics to improve genetic code expansion (GCE) in synthetic organisms.

遗传密码是细胞用来将氨基酸结合到蛋白质中的手册。可以通过细胞、分子和化学操作人为地扩展本手册，以改善蛋白质功能。体内遗传密码扩展策略与天然蛋白质合成受到相同的功能限制。在这里，我们回顾了通过操纵翻译机制将非规范氨基酸 (ncAA) 纳入设计蛋白质的方法，并在这些方法与改善现存生物体翻译的自然适应之间进行了比较。遵循这一逻辑，我们提出了新的受自然启发的策略来改善合成生物中的遗传密码扩展 (GCE)。