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Engineered tyrosyl-tRNA synthetase with the nonstandard amino acid L-4,4-biphenylalanineEngineered tyrosyl-tRNA synthetase with the nonstandard amino acid L-4,4-biphenylalanine
Structural highlights
FunctionA0A0H2UKY9_ECOLI Catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr).[HAMAP-Rule:MF_02006] Publication Abstract from PubMedGenetically modified organisms (GMOs) are increasingly deployed at large scales and in open environments. Genetic biocontainment strategies are needed to prevent unintended proliferation of GMOs in natural ecosystems. Existing biocontainment methods are insufficient because they impose evolutionary pressure on the organism to eject the safeguard by spontaneous mutagenesis or horizontal gene transfer, or because they can be circumvented by environmentally available compounds. Here we computationally redesign essential enzymes in the first organism possessing an altered genetic code (Escherichia coli strain C321.DeltaA) to confer metabolic dependence on non-standard amino acids for survival. The resulting GMOs cannot metabolically bypass their biocontainment mechanisms using known environmental compounds, and they exhibit unprecedented resistance to evolutionary escape through mutagenesis and horizontal gene transfer. This work provides a foundation for safer GMOs that are isolated from natural ecosystems by a reliance on synthetic metabolites. Biocontainment of genetically modified organisms by synthetic protein design.,Mandell DJ, Lajoie MJ, Mee MT, Takeuchi R, Kuznetsov G, Norville JE, Gregg CJ, Stoddard BL, Church GM Nature. 2015 Feb 5;518(7537):55-60. doi: 10.1038/nature14121. Epub 2015 Jan 21. PMID:25607366[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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