Hierarchical control of enzymatic actuators using DNA-based switchable memories

Lenny H.H. Meijer, Alex Joesaar, Erik Steur, Wouter Engelen, Rutger A. van Santen, Maarten Merkx, Tom F.A. de Greef

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)
124 Downloads (Pure)

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.

Original languageEnglish
Article number1117
Number of pages11
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • Algorithms
  • DNA/genetics
  • DNA, Single-Stranded/genetics
  • Enzymes/chemistry
  • Feedback
  • Feedback, Physiological
  • Gene Regulatory Networks
  • Kinetics
  • Metabolic Engineering
  • Models, Genetic
  • Signal Transduction
  • beta-Lactamases/chemistry

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