英国剑桥大学Jason W. Chin课题组发现，正义密码子重分配可产生病毒抗性和编码的聚合物合成。该项研究成果发表在2021年6月4日出版的《科学》杂志上。

研究人员表示，人们普遍假设，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造一个遗传防火墙，并使正义密码子重新分配成为可能。然而，对这些假设进行检验是不可能的。

在大肠杆菌中进行同义密码子压缩和实验室进化之后，研究人员删除了tRNA和释放因子1，它们通常可以解码两个正义密码子和一个终止密码子；由此产生的细胞无法读取经典的遗传密码，并且对病毒混合物具有完全抵抗力。研究人员重新分配了这些密码子，以便能够有效合成包含三种不同非经典氨基酸的蛋白质。

值得注意的是，研究人员证明了这些细胞可以轻松重编程，从而用于编码多种非经典杂聚物和大环化合物的翻译。

附：英文原文

Title: Sense codon reassignment enables viral resistance and encoded polymer synthesis

Author: Wesley E. Robertson, Louise F. H. Funke, Daniel de la Torre, Julius Fredens, Thomas S. Elliott, Martin Spinck, Yonka Christova, Daniele Cervettini, Franz L. Bge, Kim C. Liu, Salvador Buse, Sarah Maslen, George P. C. Salmond, Jason W. Chin

Issue&Volume: 2021/06/04

Abstract: 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.

DOI: 10.1126/science.abg3029

Source: https://science.sciencemag.org/content/372/6546/1057