Dissipatively Fueled Unidirectionally Communicating DNA Circuits That Control Biocatalysis

Angewandte Chemie, vol. 138

Abstract

ABSTRACT Unlike most synthetic systems, life constantly reorganizes itself through the irreversible consumption of energy‐rich molecules and exhibits dynamic functionalities governed by spatiotemporally controlled biocatalytic processes. Inspired by this, we herein demonstrate unidirectionally communicating, out‐of‐equilibrium DNA circuits that enable network‐guided control of the biocatalytic activity of an enzyme. The unidirectional communication is realized through the programmed, dissipative manipulation of information transfer. In this process, transient activation of a DNAzyme generates the fuel required for the temporal activation of trypsin. Prior to establishing this information‐transfer framework, we employed fuel‐driven dissipation to autonomously and temporally regulate the activity of nucleic acid and protein‐based enzymes, each operating in individual cycles. The transient state of the systems is attained through rapid hybridization of DNA strands, while digestion of the DNA fuel by exonucleases regenerates the initial equilibrium state. These processes proceed in a cyclic manner, allowing the systems to attain an out‐of‐equilibrium state. Precise control over the lifetime of this transient state was achieved by regulating external factors, such as DNA fuel and exonuclease concentrations, and internally by exploiting the toe‐hold length‐dependent digestion kinetics of the exonucleases. To establish our findings, we adopted a combined approach that includes both experimental and computational methodologies.

Authors 6

1. Daniel Felder Aachen AVT.CVT – Chair for Chemical Process Engineering DWI – Leibniz Institute for Interactive Materials Aachen Germany

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   AVT.CVT – Chair for Chemical Process Engineering RWTH Aachen University Aachen Germany

   DWI‐Leibniz Institute for Interactive Materials Aachen Germany

2. Gurudas Chakraborty Aachen DWI – Leibniz Institute for Interactive Materials Aachen Germany

   DWI – Leibniz Institute for Interactive Materials

   Affiliation as printed

   DWI‐Leibniz Institute for Interactive Materials Aachen Germany

3. Tim J. Seifert Aachen Institute of Technical and Macromolecular Chemistry

   RWTH Aachen University

   Affiliation as printed

   Institute of Technical and Macromolecular Chemistry RWTH Aachen University Aachen Germany

4. Matthias Wessling Aachen AVT.CVT – Chair for Chemical Process Engineering DWI – Leibniz Institute for Interactive Materials Aachen Germany

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   AVT.CVT – Chair for Chemical Process Engineering RWTH Aachen University Aachen Germany

   DWI‐Leibniz Institute for Interactive Materials Aachen Germany

5. Lifei Zheng

   Wenzhou Institute, University of Chinese Academy of Sciences

   Affiliation as printed

   Wenzhou Institute University of Chinese Academy of Sciences Wenzhou P.R. China

6. Andreas Herrmann Aachen DWI – Leibniz Institute for Interactive Materials Aachen Germany Institute of Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI‐Leibniz Institute for Interactive Materials Aachen Germany

   Institute of Technical and Macromolecular Chemistry RWTH Aachen University Aachen Germany