Communication and Cross‐Regulation between Chemically Fueled Sender and Receiver Reaction Networks

Nature connects multiple fuel‐driven chemical/enzymatic reaction networks (CRNs/ERNs) via cross‐regulation to hierarchically control biofunctions for a tailored adaption in complex sensory landscapes. Herein, we introduce a facile example of communication and cross‐regulation among two fuel‐driven DNA‐based ERNs regulated by a concatenated RNA transcription regulator. ERN1 (“sender”) is designed for the fuel‐driven promoter formation for T7 RNA polymerase, which activates RNA transcription. The produced RNA can deactivate or activate DNA in ERN2 (“receiver”) by toehold‐mediated strand displacement, leading to a communication between two ERNs. The RNA from ERN1 can repress or promote the fuel‐driven state of ERN2; ERN2 in turn feedbacks to regulate the lifetime of ERN1. Furthermore, the incorporation of RNase H allows for RNA degradation and enables the autonomous recovery of ERN2. We believe that concatenation of multiple CRNs/ERNs provides a basis for the design of more elaborate autonomous regulatory mechanisms in systems chemistry and synthetic biology.