Biocompatible photochemistry for the spatiotemporal control of microbial growth

Spatiotemporal control of growth is essential for the application of engineered microorganisms. The ideal method to achieve this is by employing light irradiation as it is non-invasive and can be tuned for highly specific regulation. To achieve a titratable link between microbes and light, methods have focussed on the development of light-responsive genetic elements, which possess complexities that cannot be applied universally to engineered microbes. Biocompatible chemistry is gaining interest as a tool for expanding the applications of synthetic biology, including for the regulation of microbes. Here we characterise the first biocompatible photochemical reaction as a turn-on switch for growth and showcase its application in the spatiotemporal control of microbial growth and metabolic chemistry, observing that the photo-actuated release of an o-nitrobenzyl-caged essential metabolite could be employed to rescue auxotrophic Escherichia coli in liquid culture and enable temporal control of growth rate and final cell density. This non-invasive method also allows the precise regulation of cell densities within microbial co-cultures, as well as controlling the photopatterning of bacteria on solid media. Our methodology expands the biocompatible chemistry toolkit for gene and growth regulation to enable the accurate and precise control of microbes in engineering biology.