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• W4309078087 abstract "Advances in synthetic biology, bioengineering, and computation allow us to rapidly and reliably program cells with increasingly complex and useful functions. However, because the functions we engineer cells to perform are typically burdensome to cell growth, they can be rapidly lost due to the processes of mutation and natural selection. Here, we show that a strategy of terminal differentiation improves the evolutionary stability of burdensome functions in a general manner by realizing a reproductive and metabolic division of labor. To implement this strategy, we develop a genetic differentiation circuit in Escherichia coli using unidirectional integrase-recombination. With terminal differentiation, differentiated cells uniquely express burdensome functions driven by the orthogonal T7 RNA polymerase, but their capacity to proliferate is limited to prevent the propagation of advantageous loss-of-function mutations that inevitably occur. We demonstrate computationally and experimentally that terminal differentiation increases duration and yield of high-burden expression and that its evolutionary stability can be improved with strategic redundancy. Further, we show this strategy can even be applied to toxic functions. Overall, this study provides an effective, generalizable approach for protecting burdensome engineered functions from evolutionary degradation." @default.
• W4309078087 created "2022-11-21" @default.
• W4309078087 creator A5040756158 @default.
• W4309078087 creator A5055901264 @default.
• W4309078087 date "2022-11-10" @default.
• W4309078087 modified "2023-10-13" @default.
• W4309078087 title "Integrase-mediated differentiation circuits improve evolutionary stability of burdensome and toxic functions in E. coli" @default.
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• W4309078087 doi "https://doi.org/10.1038/s41467-022-34361-y" @default.
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