A Bistable Switch in Dynamic Thiodepsipeptide Folding and Template-Directed Ligation

Bistable reaction networks provide living cells with chemically controlled mechanisms for long-term memory storage. Such networks are also often switchable and can be flipped from one state to the other. We target here a major challenge in systems chemistry research, namely developing synthetic, non-enzymatic, networks that mimic such a complex function. Therefore, we describe a dynamic network that depending on initial thiodepsipeptide concentrations leads to one of two distinct steady states. This bistable system is readily switched by applying the appropriate stimuli. The relationship between the reaction network topology and its capacity to invoke bistability is then analyzed by control experiments and theory. We suggest that demonstrating bistable behavior using synthetic networks further highlights their possible role in early evolution, and may shine light on potential utility for novel applications, such as chemical memories.