It is widely hypothesized that removing cellular transfer RNAs (tRNAs)—making their cognate codons unreadable—might create a genetic firewall to viral infection and enable sense codon reassignment. However, it has been impossible to test these hypotheses. In this work, following synonymous codon compression and laboratory evolution in Escherichia coli, we deleted the tRNAs and release factor 1, which normally decode two sense codons and a stop codon; the resulting cells could not read the canonical genetic code and were completely resistant to a cocktail of viruses. We reassigned these codons to enable the efficient synthesis of proteins containing three distinct noncanonical amino acids. Notably, we demonstrate the facile reprogramming of our cells for the encoded translation of diverse noncanonical heteropolymers and macrocycles.

人们普遍认为，去除细胞转移 RNA (tRNA)——使它们的同源密码子不可读——可能会为病毒感染创建一个遗传防火墙，并实现有义密码子的重新分配。然而，要检验这些假设是不可能的。在这项工作中，遵循大肠杆菌中的同义密码子压缩和实验室进化，我们删除了 tRNA 并释放因子 1，它通常解码两个有义密码子和一个终止密码子；由此产生的细胞无法读取典型的遗传密码，并且完全抵抗病毒混合物。我们重新分配了这些密码子，以便能够有效合成含有三种不同的非常规氨基酸的蛋白质。值得注意的是，我们证明了我们的细胞可以轻松重新编程，以编码翻译各种非规范杂聚物和大环化合物。