Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06511; email:
Department of Biochemistry, University of Washington, Seattle, Washington 98195.
Annu Rev Microbiol. 2017 Sep 8;71:557-577. doi: 10.1146/annurev-micro-090816-093247. Epub 2017 Jul 11.
The genetic code-the language used by cells to translate their genomes into proteins that perform many cellular functions-is highly conserved throughout natural life. Rewriting the genetic code could lead to new biological functions such as expanding protein chemistries with noncanonical amino acids (ncAAs) and genetically isolating synthetic organisms from natural organisms and viruses. It has long been possible to transiently produce proteins bearing ncAAs, but stabilizing an expanded genetic code for sustained function in vivo requires an integrated approach: creating recoded genomes and introducing new translation machinery that function together without compromising viability or clashing with endogenous pathways. In this review, we discuss design considerations and technologies for expanding the genetic code. The knowledge obtained by rewriting the genetic code will deepen our understanding of how genomes are designed and how the canonical genetic code evolved.
遗传密码——细胞用于将其基因组翻译成执行许多细胞功能的蛋白质的语言——在整个自然生命中高度保守。重写遗传密码可能会产生新的生物学功能,例如用非标准氨基酸 (ncAAs) 扩展蛋白质化学,并将合成生物体与天然生物体和病毒从遗传上隔离。使带有 ncAAs 的蛋白质瞬时产生一直是可能的,但是稳定扩展的遗传密码以在体内持续发挥功能需要一种综合方法:创建重新编码的基因组并引入新的翻译机制,这些机制共同发挥作用而不会损害生存能力或与内源性途径发生冲突。在这篇综述中,我们讨论了扩展遗传密码的设计考虑因素和技术。通过重写遗传密码获得的知识将加深我们对基因组如何设计以及经典遗传密码如何进化的理解。