Sense codon reassignment enables viral resistance and encoded polymer synthesis

被引：139

作者：

Robertson, Wesley E. ^{[1
]}

Funke, Louise F. H. ^{[1
]}

de la Torre, Daniel ^{[1
]}

Fredens, Julius ^{[1
]}

Elliott, Thomas S. ^{[1
]}

Spinck, Martin ^{[1
]}

Christova, Yonka ^{[1
]}

Cervettini, Daniele ^{[1
]}

Boge, Franz L. ^{[1
]}

Liu, Kim C. ^{[1
]}

Buse, Salvador ^{[1
]}

Maslen, Sarah ^{[1
]}

Salmond, George P. C. ^{[2
]}

Chin, Jason W. ^{[1
]}

机构：

[1] MRC, Lab Mol Biol, Cambridge, England

[2] Univ Cambridge, Dept Biochem, Cambridge, England

来源：

SCIENCE | 2021年 / 372卷 / 6546期

基金：

英国医学研究理事会;

关键词：

UNNATURAL AMINO-ACIDS; GENETIC-CODE; IN-VIVO; IDENTIFICATION;

D O I：

10.1126/science.abg3029

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1057 / +

页数：49

共 42 条

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