Genomically Recoded Organisms Expand Biological Functions
By M. Lajoie, Alexis J. Rovner, Daniel B. Goodman, Hans R. Aerni, A. Haimovich, Gleb Kuznetsov, Jaron A. M. Mercer, Harris H. Wang, P. Carr, Joshua A. Mosberg and 6 more. Science, 2013
779 citations recorded by the source corpus.
Changing the Code Easily and efficiently expanding the genetic code could provide tools to genome engineers with broad applications in medicine, energy, agriculture, and environmental safety. Lajoie et al. (p. 357) replaced all known UAG stop codons with synonymous UAA stop codons in Escherichia coli MG1655, as well as release factor 1 (RF1; terminates translation at UAG), thereby eliminating natural UAG translation function without impairing fitness. This made it possible to reassign UAG as a dedicated codon to genetically encode nonstandard amino acids while avoiding deleterious incorporation at native UAG positions. The engineered E. coli incorporated nonstandard amino acids into its proteins and showed enhanced resistance to bacteriophage T7. In a second paper, Lajoie et al. (p. 361) demonstrated the recoding of 13 codons in 42 highly expressed essential genes in E. coli. Codon usage was malleable, but synonymous codons occasionally were nonequivalent in unpredictable ways. Bacteria engineered to use nonstandard amino acids show increased resistance to bacteriophage attack. We describe the construction and characterization of a genomically recoded organism (GRO). We replaced all known UAG stop codons in Escherichia coli MG1655 with synonymous UAA codons, which permitted the deletion of release factor 1 and reassignment of UAG translation function. This GRO exhibited improved properties for incorporation of nonstandard amino acids that expand the chemical diversity of proteins in vivo. The GRO also exhibited increased resistance to T7 bacteriophage, demonstrating that new genetic codes could enable increased viral resistance.
Subfields: Genetics, Molecular Biology, Plant Science
View Paper: https://www.semanticscholar.org/paper/16e01e97deb1c7553fab75878570b7aa26a02543
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Citations in the corpus
- Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use (2016, neutral): “In contrast to this use for naturally occurring organisms, the same word was later used somewhat differently in connection with human intervention to ‘genomically recode organisms’ (719), though several of the authors involved are now using a different term for that meaning (720).”
- Design and synthesis of a minimal bacterial genome (2016, background): “For example, a cell could be designed with added metabolic pathways (34), an altered genetic code (35), or dramatically al-”