Design of a Synthetic Integral Feedback Circuit: Dynamic Analysis and DNA Implementation

The design and implementation of regulation motifs ensuring robust perfect adaptation are challenging problems in synthetic biology. Indeed, the design of high-yield robust metabolic pathways producing, for instance, drug precursors and biofuels, could be easily imagined to rely on such a control strategy in order to optimize production levels and reduce production costs, despite the presence of environmental disturbance and model uncertainty. We propose here a motif that ensures tracking and robust perfect adaptation for the controlled reaction network through integral feedback. Its metabolic load on the host is fully tunable and can be made arbitrarily close to the constitutive limit, the universal minimal metabolic load of all possible controllers. A DNA implementation of the controller network is finally provided. Computer simulations using realistic parameters demonstrate the good agreement between the DNA implementation and the ideal controller dynamics.