Synthetic Biology and Control Theory: Designing Synthetic Biomolecular Controllers by Exploiting Dynamic Covalent Modification Cycle with Positive Autoregulation Properties

Abstract

The emerging field at the intersection of synthetic biology, network modelling, and control theory has grown in popularity in recent years. In this study, the aim is to design synthetic biomolecular controllers by exploiting the covalent modification cycle (CMC) enhanced with direct and indirect positive autoregulation (DPAR and IPAR). Two novel biomolecular controllers proposed, the Brink controller (BC) with DPAR (namely BC-DPAR) and the BC with IPAR (namely BC-IPAR), allow to (a) use fewer chemical reactions than purely designs based on dual chemical reaction networks (DCRNs), and (b) improve the stability of ultrasensitive response when designing biomolecular controllers. Following the conversion route from chemical reactions to DNA strand displacements, the integration of the two novel controllers and an enzymatic proteolysis model proposed aims to analyse the regulatory properties by exploring the tracking response of proteolysis products.