Hierarchical control of enzymatic actuators using DNA-based switchable memories

Article

Meijer, Lenny H.H., Joesaar, Alex, Steur, Erik, Engelen, Wouter, Van Santen, Rutger A., Merkx, Maarten & De Greef, Tom F.A. (2017). Hierarchical control of enzymatic actuators using DNA-based switchable memories. Nature Communications, 8(1):1117 In Scopus Cited 0 times.

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Abstract

 

Inspired by signaling networks in living cells, DNA-based programming aims for the engineering of biochemical networks capable of advanced regulatory and computational functions under controlled cell-free conditions. While regulatory circuits in cells control downstream processes through hierarchical layers of signal processing, coupling of enzymatically driven DNA-based networks to downstream processes has rarely been reported. Here, we expand the scope of molecular programming by engineering hierarchical control of enzymatic actuators using feedback-controlled DNA-circuits capable of advanced regulatory dynamics. We developed a translator module that converts signaling molecules from the upstream network to unique DNA strands driving downstream actuators with minimal retroactivity and support these findings with a detailed computational analysis. We show our modular approach by coupling of a previously engineered switchable memories circuit to downstream actuators based on β-lactamase and luciferase. To the best of our knowledge, our work demonstrates one of the most advanced DNA-based circuits regarding complexity and versatility.