Exploiting natural chemical photosensitivity of anhydrotetracycline and tetracycline for dynamic and setpoint chemo-optogenetic control

The transcriptional inducer anhydrotetracycline (aTc) and the bacteriostatic antibiotic tet-
racycline (Tc) are commonly used in all fields of biology for control of transcription or
translation. A drawback of these and other small molecule inducers is the difficulty of their
removal from cell cultures, limiting their application for dynamic control. Here, we describe a
simple method to overcome this limitation, and show that the natural photosensitivity of aTc/
Tc can be exploited to turn them into highly predictable optogenetic transcriptional- and
growth-regulators. This new optogenetic class uniquely features both dynamic and setpoint
control which act via population-memory adjustable through opto-chemical modulation. We
demonstrate this method by applying it for dynamic gene expression control and for
enhancing the performance of an existing optogenetic system. We then expand the utility of
the aTc system by constructing a new chemical bandpass filter that increases its aTc
response range. The simplicity of our method enables scientists and biotechnologists to use
their existing systems employing aTc/Tc for dynamic optogenetic experiments without
genetic modification.