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bioRxiv · 10.1101/170951

A synthetic integral feedback controller for robust tunable regulation in bacteria

Lillacci, G.·Aoki, S. K.·Schweingruber, D.·Khammash, M.
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Abstract

We report on the first engineered integral feedback control system in a living cell. The controller is based on the recently published antithetic integral feedback motif [1] which has been analytically shown to have favorable regulation properties. It is implemented along with test circuitry in Escherichia coli using seven genes and three small-molecule inducers. The closed-loop system is highly tunable, allowing a regulated protein of interest to be driven to a desired level and maintained there with precision. Realized using a sigma/anti-sigma protein pair, the integral controller ensures that regulation is maintained in the face of perturbations that lead to the regulated proteins degradation, thus serving as a proof-of-concept prototype of integral feedback implementation in living cells. When suitably optimized, this integral controller may be utilized as a general-purpose robust regulator for genetic circuits with unknown or partially-known topologies and parameters.

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Lillacci, G., Aoki, S. K., Schweingruber, D., Khammash, M.. 2017-08-01. A synthetic integral feedback controller for robust tunable regulation in bacteria. https://doi.org/10.1101/170951

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