Publication Date:
2015-01-22
Description:
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.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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422498/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422498/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- R01 GM049857/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2015 Feb 5;518(7537):55-60. doi: 10.1038/nature14121. Epub 2015 Jan 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Program in Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; 1] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA. ; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. ; 1] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25607366" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acids/*chemistry/*metabolism
;
Biological Evolution
;
Codon/genetics
;
Containment of Biohazards/*methods
;
Ecosystem
;
Escherichia coli/enzymology/*genetics/growth & development/*metabolism
;
Escherichia coli Proteins/*biosynthesis/genetics/metabolism
;
Gene Transfer, Horizontal/genetics
;
Genes, Essential/genetics
;
Genetic Code/genetics
;
Genetic Engineering/methods
;
Microbial Viability/genetics
;
Mutation/genetics
;
Organisms, Genetically Modified/*genetics/metabolism
;
Safety
;
Selection, Genetic
;
Synthetic Biology/*methods
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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