Sense codon reassignment enables viral resistance and encoded polymer synthesis
- 4 June 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 372 (6546), 1057-1062
- https://doi.org/10.1126/science.abg3029
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.Funding Information
- Medical Research Council (MC_UP_A024_1008)
- Medical Research Council (MC_U105181009)
- European Research Council (SGCR)
- Development Gap Fund Award (P2019-0003)
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