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Auxotrophy to Xeno-DNA : an exploration of combinatorial mechanisms for a high-fidelity biosafety system for synthetic biology applications

Auxotrophy to Xeno-DNA : an exploration of combinatorial mechanisms for a high-fidelity biosafety system for synthetic biology applications

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WHITFORD, Christopher M., Saskia DYMEK, Denise KERKHOFF, Camilla MÄRZ, Olga SCHMIDT, Maximilian EDICH, Julian DROSTE, Boas PUCKER, Christian RÜCKERT, Jörn KALINOWSKI, 2018. Auxotrophy to Xeno-DNA : an exploration of combinatorial mechanisms for a high-fidelity biosafety system for synthetic biology applications. In: Journal of Biological Engineering. 12(1), 13. eISSN 1754-1611. Available under: doi: 10.1186/s13036-018-0105-8

@article{Whitford2018Auxot-48115, title={Auxotrophy to Xeno-DNA : an exploration of combinatorial mechanisms for a high-fidelity biosafety system for synthetic biology applications}, year={2018}, doi={10.1186/s13036-018-0105-8}, number={1}, volume={12}, journal={Journal of Biological Engineering}, author={Whitford, Christopher M. and Dymek, Saskia and Kerkhoff, Denise and März, Camilla and Schmidt, Olga and Edich, Maximilian and Droste, Julian and Pucker, Boas and Rückert, Christian and Kalinowski, Jörn}, note={Article Number: 13} }

Dymek, Saskia Kerkhoff, Denise eng Dymek, Saskia 2019-12-19T09:24:17Z Droste, Julian Rückert, Christian Kerkhoff, Denise 2018 terms-of-use Schmidt, Olga Whitford, Christopher M. Kalinowski, Jörn Schmidt, Olga Edich, Maximilian Kalinowski, Jörn Edich, Maximilian Pucker, Boas Whitford, Christopher M. Rückert, Christian März, Camilla März, Camilla Background<br />Biosafety is a key aspect in the international Genetically Engineered Machine (iGEM) competition, which offers student teams an amazing opportunity to pursue their own research projects in the field of Synthetic Biology. iGEM projects often involve the creation of genetically engineered bacterial strains. To minimize the risks associated with bacterial release, a variety of biosafety systems were constructed, either to prevent survival of bacteria outside the lab or to hinder horizontal or vertical gene transfer.<br /><br />Main body<br />Physical containment methods such as bioreactors or microencapsulation are considered the first safety level. Additionally, various systems involving auxotrophies for both natural and synthetic compounds have been utilized by iGEM teams in recent years. Combinatorial systems comprising multiple auxotrophies have been shown to reduced escape frequencies below the detection limit. Furthermore, a number of natural toxin-antitoxin systems can be deployed to kill cells under certain conditions. Additionally, parts of naturally occurring toxin-antitoxin systems can be used for the construction of ‘kill switches’ controlled by synthetic regulatory modules, allowing control of cell survival. Kill switches prevent cell survival but do not completely degrade nucleic acids. To avoid horizontal gene transfer, multiple mechanisms to cleave nucleic acids can be employed, resulting in ‘self-destruction’ of cells. Changes in light or temperature conditions are powerful regulators of gene expression and could serve as triggers for kill switches or self-destruction systems. Xenobiology-based containment uses applications of Xeno-DNA, recoded codons and non-canonical amino acids to nullify the genetic information of constructed cells for wild type organisms. A ‘minimal genome’ approach brings the opportunity to reduce the genome of a cell to only genes necessary for survival under lab conditions. Such cells are unlikely to survive in the natural environment and are thus considered safe hosts. If suitable for the desired application, a shift to cell-free systems based on Xeno-DNA may represent the ultimate biosafety system.<br /><br />Conclusion<br />Here we describe different containment approaches in synthetic biology, ranging from auxotrophies to minimal genomes, which can be combined to significantly improve reliability. Since the iGEM competition greatly increases the number of people involved in synthetic biology, we will focus especially on biosafety systems developed and applied in the context of the iGEM competition. Droste, Julian Auxotrophy to Xeno-DNA : an exploration of combinatorial mechanisms for a high-fidelity biosafety system for synthetic biology applications Pucker, Boas 2019-12-19T09:24:17Z

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