Tuning the dynamic range of bacterial promoters regulated by ligand-inducible transcription factors
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One challenge for synthetic biologists is the predictable tuning of genetic circuit regulatory components to elicit desired outputs. Gene expression driven by ligand-inducible transcription factor systems must exhibit the correct ON and OFF characteristics: appropriate activation and leakiness in the presence and absence of inducer, respectively. However, the dynamic range of a promoter (i.e., absolute difference between ON and OFF states) is difficult to control. We report a method that tunes the dynamic range of ligand-inducible promoters to achieve desired ON and OFF characteristics. We build combinatorial sets of AraC-and LasR-regulated promoters containing -10 and -35 sites from synthetic and Escherichia coli promoters. Four sequence combinations with diverse dynamic ranges were chosen to build multi-input transcriptional logic gates regulated by two and three ligand-inducible transcription factors (LacI, TetR, AraC, XylS, RhlR, LasR, and LuxR). This work enables predictable control over the dynamic range of regulatory components.
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Chen, Ye, Ho, Joanne M.L., Shis, David L., et al.. "Tuning the dynamic range of bacterial promoters regulated by ligand-inducible transcription factors." Nature Communications, 9, (2018) Springer Nature: https://doi.org/10.1038/s41467-017-02473-5.