Circadian clocks go in vitro: purely post-translational oscillators in cyanobacteria

Recent findings about the core of the circadian oscillator in cyanobacteria are challenging the dogma that such clocks are driven through transcriptional–translational feedback regulation. Instead, the master pacemaker is independent of both transcription and translation, and consists of self-sustained oscillations in the phosphorylation status of the KaiC protein in vivo. Using a minimal cocktail of three recombinant proteins with adenosine triphosphate, the core clock was even reproduced in vitro. The so-born chemical oscillator could reproduce accurately temperature compensation and altered period phenotypes in mutants. This system now provides an ideal playground for rebuilding the circadian clock by adding successive components while understanding every single step with chemical resolution.