Controlling the Cyanobacterial Clock by Synthetically Rewiring Metabolism

•Expressing a transgenic sugar transporter in cyanobacteria allows growth in the dark•Glucose feeding overrides the effect of darkness on the circadian clock•In complete darkness, the KaiABC clock senses rhythmic feeding•Metabolism is the fundamental synchronizer for the cyanobacterial clock

SummaryCircadian clocks are oscillatory systems that allow organisms to anticipate rhythmic changes in the environment. Several studies have shown that circadian clocks are connected to metabolism, but it is not generally clear whether metabolic signaling is one voice among many that influence the clock or whether metabolic cycling is the major clock synchronizer. To address this question in cyanobacteria, we used a synthetic biology approach to make normally autotrophic cells capable of growth on exogenous sugar. This allowed us to manipulate metabolism independently from light and dark. We found that feeding sugar to cultures blocked the clock-resetting effect of a dark pulse. Furthermore, in the absence of light, the clock efficiently synchronizes to metabolic cycles driven by rhythmic feeding. We conclude that metabolic activity, independent of its source, is the primary clock driver in cyanobacteria.

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