Hierarchical control of enzymatic actuators using DNA-based switchable memories

Lenny H. H. Meijer, Alex Joesaar, Erik Steur, Wouter Engelen, Rutger A. Santen, Maarten Merkx and Tom F. A. Greef ()
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Lenny H. H. Meijer: Eindhoven University of Technology
Alex Joesaar: Eindhoven University of Technology
Erik Steur: Eindhoven University of Technology
Wouter Engelen: Eindhoven University of Technology
Rutger A. Santen: Eindhoven University of Technology
Maarten Merkx: Eindhoven University of Technology
Tom F. A. Greef: Eindhoven University of Technology

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01127-w

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