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.