Biocontainment of genetically modified organisms by synthetic protein design

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.

doi:10.1038/nature14121

Title: Biocontainment of genetically modified organisms by synthetic protein design

Journal Article · Tue Jan 20 23:00:00 EST 2015 · Nature (London)

DOI: https://doi.org/10.1038/nature14121 · OSTI ID:1347113

Mandell, Daniel J. ^[1]; Lajoie, Marc J. ^[2]; Mee, Michael T. ^[3]; Takeuchi, Ryo ^[4]; Kuznetsov, Gleb ^[5]; Norville, Julie E. ^[5]; Gregg, Christopher J. ^[5]; Stoddard, Barry L. ^[6]; Church, George M. ^[7]

Harvard Medical School, Boston, MA (United States). Dept. of Genetics; Office of Scientific and Technical Information (OSTI)
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
Harvard Medical School, Boston, MA (United States). Dept. of Genetics
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

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.

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Research Organization:: Harvard Univ., Boston, MA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)

Grant/Contract Number:: FG02-02ER63445

OSTI ID:: 1347113

Journal Information:: Nature (London), Journal Name: Nature (London) Journal Issue: 7537 Vol. 518; ISSN 0028-0836

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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An engineered bacterium auxotrophic for an unnatural amino acid: a novel biological containment system Kato, Yusuke https://doi.org/10.7287/peerj.preprints.1001	posted_content	April 2015
An engineered bacterium auxotrophic for an unnatural amino acid: a novel biological containment system Kato, Yusuke https://doi.org/10.7287/peerj.preprints.1001v1	preprint	April 2015
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