Abstract In this work, we explore the refactoring of the circuitry of ???? phage by engineering a new-to-nature regulator that responds to an ad hoc input signal that behaves orthogonal with respect to the host cell. We tailored a chimeric regulator, termed Q ???? , between the CI protein of the ???? phage and the BzdR repressor from Azoarcus sp. strain CIB that responds to benzoyl-CoA. When the Q ???? was expressed in the appropriate Escherichia coli cells, it was able to reprogram the lytic/lysogenic ???? phage decision according to the intracellular production of benzoyl-CoA. Our results are also an example of how generating new artificial regulators that respond to effectors of choice may be useful to control different cellular processes.
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