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. In this paper, 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. Finally, this work provides a foundation for safer GMOs that are isolated from natural ecosystems by a reliance on synthetic metabolites.
- Authors:
-
- Harvard Medical School, Boston, MA (United States). Dept. of Genetics
- Harvard Medical School, Boston, MA (United States). Dept. of Genetics; Harvard Univ., Cambridge, MA (United States). Program in Chemical Biology
- Harvard Medical School, Boston, MA (United States). Dept. of Genetics; Boston Univ., MA (United States). Dept. of Biomedical Engineering
- Fred Hutchinson Cancer Research Center, Seattle, WA (United States). Division of Basic Sciences
- Fred Hutchinson Cancer Research Center, Seattle, WA (United States). Division of Basic Science
- Harvard Medical School, Boston, MA (United States). Dept. of Genetics; Harvard Univ., Cambridge, MA (United States). Wyss Inst. for Biologically Inspired Engineering
- Publication Date:
- Research Org.:
- Harvard Univ., Cambridge, MA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1347113
- Grant/Contract Number:
- FG02-02ER63445
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature (London)
- Additional Journal Information:
- Journal Name: Nature (London); Journal Volume: 518; Journal Issue: 7537; Journal ID: ISSN 0028-0836
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; genetics; biotechnology; molecular evolution; computational biology and bioinformatics
Citation Formats
Mandell, Daniel J., Lajoie, Marc J., Mee, Michael T., Takeuchi, Ryo, Kuznetsov, Gleb, Norville, Julie E., Gregg, Christopher J., Stoddard, Barry L., and Church, George M. Biocontainment of genetically modified organisms by synthetic protein design. United States: N. p., 2015.
Web. doi:10.1038/nature14121.
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. Biocontainment of genetically modified organisms by synthetic protein design. United States. https://doi.org/10.1038/nature14121
Mandell, Daniel J., Lajoie, Marc J., Mee, Michael T., Takeuchi, Ryo, Kuznetsov, Gleb, Norville, Julie E., Gregg, Christopher J., Stoddard, Barry L., and Church, George M. Wed .
"Biocontainment of genetically modified organisms by synthetic protein design". United States. https://doi.org/10.1038/nature14121. https://www.osti.gov/servlets/purl/1347113.
@article{osti_1347113,
title = {Biocontainment of genetically modified organisms by synthetic protein design},
author = {Mandell, Daniel J. and Lajoie, Marc J. and Mee, Michael T. and Takeuchi, Ryo and Kuznetsov, Gleb and Norville, Julie E. and Gregg, Christopher J. and Stoddard, Barry L. and Church, George M.},
abstractNote = {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. In this paper, 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. Finally, this work provides a foundation for safer GMOs that are isolated from natural ecosystems by a reliance on synthetic metabolites.},
doi = {10.1038/nature14121},
journal = {Nature (London)},
number = 7537,
volume = 518,
place = {United States},
year = {Wed Jan 21 00:00:00 EST 2015},
month = {Wed Jan 21 00:00:00 EST 2015}
}
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Author Correction: Precise control of SCRaMbLE in synthetic haploid and diploid yeast
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Towards Biocontained Cell Factories: An Evolutionarily Adapted Escherichia coliStrain Produces a New-to-nature Bioactive Lantibiotic ContainingThienopyrrole-Alanine
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A Novel Biocontainment Strategy Makes Bacterial Growth and Survival Dependent on Phosphite
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Engineering posttranslational proofreading to discriminate nonstandard amino acids
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Large-scale recoding of a bacterial genome by iterative recombineering of synthetic DNA
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Improved sgRNA design in bacteria via genome-wide activity profiling
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Population dynamics of synthetic terraformation motifs
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Millstone: Software for Multiplex Microbial Genome Analysis and Engineering
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Systems metabolic engineering as an enabling technology in accomplishing sustainable development goals
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Refactoring the Genetic Code for Increased Evolvability
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Fermentation of lactose to ethanol in cheese whey permeate and concentrated permeate by engineered Escherichia coli
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Rewriting the blueprint of life by synthetic genomics and genome engineering
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Recent advances in synthetic biosafety
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A computational approach for designing D-proteins with non-canonical amino acid optimised binding affinity
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Microbial control of arthropod-borne disease
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Auxotrophy to Xeno-DNA: an exploration of combinatorial mechanisms for a high-fidelity biosafety system for synthetic biology applications
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Commentary: Synthetic Addiction Extends the Productive Life Time of Engineered Escherichia coli Populations
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Transcription factor-based biosensors enlightened by the analyte
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Transgene Biocontainment Strategies for Molecular Farming
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Translational Control using an Expanded Genetic Code
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Coevolution Theory of the Genetic Code at Age Forty: Pathway to Translation and Synthetic Life
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