Towards a synthetic post-translational protein oscillator

Synthetic protein circuits have the potential to significantly change the landscape of biomimicry engineering. While synthetic gene circuits have already borne fruit over the past several decades, post-translational circuits engineered to bypass transcription/translation machinery can offer more immediate responses and more direct coupling to endogenous systems. However, engineering dynamic phenomena such as oscillations in these circuits remains an outstanding challenge. Only a few known biological systems, such as the KaiABC system regulating the circadian clock in cyanobacteria, offer examples of post-translational oscillators, creating a need for theoretical work to fill in the gaps. Here, we develop two distinct post-translational oscillators, each using a small number of components which interact only through reversible binding and phosphorylation/dephosphorylation reactions. Our designed oscillators rely on the self-assembly of two protein species into multimeric functional enzymes which respectively interfere with and enhance this self-assembly. We will describe the systems, the intuition behind them, and their dependence on the (few) kinetic parameters.