Biocontainment of genetically modified organisms by synthetic protein design

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...

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Bibliographic Details
Published in:	Nature (London) 2015-02, Vol.518 (7537), p.55-60
Main Authors:	Mandell, Daniel J, Lajoie, Marc J, Mee, Michael T, Takeuchi, Ryo, Kuznetsov, Gleb, Norville, Julie E, Gregg, Christopher J, Stoddard, Barry L, Church, George M
Format:	Article
Language:	eng
Subjects:	Amino Acids - chemistry Amino Acids - metabolism BASIC BIOLOGICAL SCIENCES Biological Evolution biotechnology Codon - genetics computational biology and bioinformatics Containment of Biohazards - methods Design Ecosystem Escherichia coli - enzymology Escherichia coli - genetics Escherichia coli - growth & development Escherichia coli - metabolism Escherichia coli Proteins - biosynthesis Escherichia coli Proteins - genetics Escherichia coli Proteins - metabolism Gene Transfer, Horizontal - genetics Genes Genes, Essential - genetics Genetic Code - genetics Genetic engineering Genetic Engineering - methods genetics Metabolites Microbial Viability - genetics molecular evolution Mutation Mutation - genetics Organisms Organisms, Genetically Modified - genetics Organisms, Genetically Modified - metabolism Proteins Safety Selection, Genetic Synthetic Biology - methods
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Summary:	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.
ISSN:	0028-0836 1476-4687