摘要：The design and implementation of biomolecular feedback control strategies embedded within large biomolecular synthetic systems is one of the key areas of Synthetic Biology. Many important challenges remain to be addressed. Among them, the lack of realizations of existing control algorithms through available biomolecular devices. Thus, proportional-integral controllers, one of the basic widely-used control strategies has been elusive for a long time. Recently, the antithetic sequestration-based motif has been shown to ensure robust perfect adaptation under mild assumptions and has been combined to implement proportional-integral feedback strategies. Yet, windup caused either by limitations in the process to be controlled or, most often, to restrictions in the actuator is a common problem of feedback control strategies with integral action. Saturation of signals is a limitation inherent to the biomolecular implementation of most circuits. Therefore, windup is a potential problem in biomolecular antithetic-based PI controllers. Reference conditioning, that is, dynamically providing a feasible set-point has been successfully used to tackle with the control of systems with control or state limitations. Here, we propose a reference conditioning scheme with application to the antithetic PI biomolecular controller. We show how the scheme is able to deal with windup due to either large excursions in the desired set-point or limitations caused by an increased metabolic burden in the cell.
