Exploiting the dynamic properties of covalent modification cycle for the design of synthetic analog biomolecular circuitry

Mathias Foo, Rucha Sawlekar, Declan G. Bates

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    7 Citations (Scopus)
    35 Downloads (Pure)


    Cycles of covalent modification are ubiquitous motifs in cellular signalling. Although such signalling cycles are implemented via a highly concise set of chemical reactions, they have been shown to be capable of producing multiple distinct input-output mapping behaviours – ultrasensitive, hyperbolic, signal-transducing and threshold-hyperbolic. In this paper, we show how the set of chemical reactions underlying covalent modification cycles can be exploited for the design of synthetic analog biomolecular circuitry. We show that biomolecular circuits based on the dynamics of covalent modification cycles allow (a) the computation of nonlinear operators using far fewer chemical reactions than purely abstract designs based on chemical reaction network theory, and (b) the design of nonlinear feedback controllers with strong performance and robustness properties. Our designs provide a more efficient route for translation of complex circuits and systems from chemical reactions to DNA strand displacement-based chemistry, thus facilitating their experimental implementation in future Synthetic Biology applications.
    Original languageEnglish
    Article number10
    Number of pages17
    JournalJournal of Biological Engineering
    Issue number15
    Publication statusPublished - 14 Nov 2016

    Bibliographical note

    This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.


    • Analog synthetic biomolecular circuits
    • Chemical reaction networks
    • Covalent modification cycle
    • Feedback control systems
    • Linear and nonlinear operators
    • Synthetic biology applications


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