4OUD

Engineered tyrosyl-tRNA synthetase with the nonstandard amino acid L-4,4-biphenylalanine

Summary for 4OUD

• Entry DOI: 10.2210/pdb4oud/pdb
• Descriptor: Tyrosyl-tRNA synthetase, TYROSINE, ... (4 entities in total)
• Functional Keywords: complex with l-tyrosine, rossmann fold, ligase, trna
• Biological source: Escherichia coli; More
• Cellular location: Cytoplasm : U6N9P2 U6N9P2
• Total number of polymer chains: 2
• Total formula weight: 91111.12

Authors

Takeuchi, R.,Mandell, D.J.,Lajoie, M.J.,Church, G.M.,Stoddard, B.L. (deposition date: 2014-02-16, release date: 2015-01-28, Last modification date: 2023-09-20)

Primary citation

Mandell, D.J.,Lajoie, M.J.,Mee, M.T.,Takeuchi, R.,Kuznetsov, G.,Norville, J.E.,Gregg, C.J.,Stoddard, B.L.,Church, G.M.
Biocontainment of genetically modified organisms by synthetic protein design.
Nature, 518:55-60, 2015

PubMed Abstract: Genetically 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.ΔA) 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.

PubMed: 25607366
DOI: 10.1038/nature14121

Experimental method

X-RAY DIFFRACTION (2.65 Å)