Stabilization of antithetic control via molecular buffering

A key goal in synthetic biology is the construction of molecular circuits that robustly adapt to perturbations. Although many natural systems display perfect adaptation, whereby stationary molecular concentrations are insensitive to perturbations, its engineering has proven elusive. The discovery of...

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Bibliographic Details
Published in:Journal of the Royal Society interface 2022-03, Vol.19 (188), p.20210762-20210762
Main Authors: Hancock, Edward J, Oyarzún, Diego A
Format: Article
Language:English
Subjects:
Acclimatization
Adaptation, Physiological
Homeostasis
Life Sciences–Mathematics interface
Models, Biological
Synthetic Biology
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Summary:A key goal in synthetic biology is the construction of molecular circuits that robustly adapt to perturbations. Although many natural systems display perfect adaptation, whereby stationary molecular concentrations are insensitive to perturbations, its engineering has proven elusive. The discovery of the antithetic control motif was a significant step towards a universal mechanism for engineering perfect adaptation. Antithetic control provides perfect adaptation in a wide range of systems, but it can lead to oscillatory dynamics due to loss of stability; moreover, it can lose perfect adaptation in fast growing cultures. Here, we introduce an extended antithetic control motif that resolves these limitations. We show that molecular buffering, a widely conserved mechanism for homeostatic control in Nature, stabilizes oscillations and allows for near-perfect adaptation during rapid growth. We study multiple buffering topologies and compare their performance in terms of their stability and adaptation properties. We illustrate the benefits of our proposed strategy in exemplar models for biofuel production and growth rate control in bacterial cultures. Our results provide an improved circuit for robust control of biomolecular systems.
ISSN:1742-5662
1742-5689
1742-5662
DOI:10.1098/rsif.2021.0762