Functional predictability of universal gene circuits in diverse microbial hosts

Abstract

Although the principles of synthetic biology were initially established in model bacteria, microbial producers, extremophiles and gut microbes have now emerged as valuable prokaryotic chassis for biological engineering. Extending the host range in which designed circuits can function reliably and predictably presents a major challenge for the concept of synthetic biology to materialize. In this work, we systematically characterized the cross-species universality of two transcriptional regulatory modules—the T7 RNA polymerase activator module and the repressors module—in three non-model microbes. We found striking linear relationships in circuit activities among different organisms for both modules. Parametrized model fitting revealed host non-specific parameters defining the universality of both modules. Lastly, a genetic NOT gate and a band-pass filter circuit were constructed from these modules and tested in non-model organisms. Combined models employing host non-specific parameters were successful in quantitatively predicting circuit behaviors, underscoring the potential of universal biological parts and predictive modeling in synthetic bioengineering.

Keywords

circuit predictability / host-independent genetic circuits / host-nonspecific parameters / parts characterization / transcriptional regulatory modules

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2024 The Authors. Quantitative Biology published by John Wiley & Sons Australia, Ltd on behalf of Higher Education Press.