Title
Biocontainment of genetically modified organisms by synthetic protein design.
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.Delta A) 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.
Year
DOI
Venue
2015
10.1038/nature14121
NATURE
Keywords
Field
DocType
Genetics, Biotechnology, Molecular evolution, Computational biology and bioinformatics
Biocontainment,Biology,Amino acid,Molecular evolution,Genetic code,Genetically modified organism,Genetics,Escherichia coli,Synthetic biology,Mutation
Journal
Volume
Issue
ISSN
518
7537
0028-0836
Citations 
PageRank 
References 
4
1.06
4
Authors
9