A single phosphatase can convert a robust step response into a graded, tunable or adaptive response

Abstract

Many biological signalling pathways have evolved to produce responses to environmental signals that are robust to fluctuations in protein copy number and noise. Whilst beneficial for biology, this robustness can be problematic for synthetic biologists wishing to re-engineer and subsequently tune the response of a given system. Here we show that the well-characterized EnvZ/OmpR twocomponent signalling system from Escherichia coli possesses one such robust step response. However, the synthetic addition of just a single component into the system, an extra independently controllable phosphatase, can change this behaviour to become graded and tunable, and even show adaptation. Our approach introduces a new design principle which can be implemented simply in engineering and redesigning fast signal transduction pathways for synthetic biology.

High-frequency Noise Attenuation of a Two-component System Responding to Short-pulse Input

“…The variable regions for parameters are defined in Table 1. Igoshin et al previously complied the reaction rates of EnvZ autophosphorylation, EnvZ-OmpR binding, and other steps [6]. The parameters of our model integrate some reactions and reflect the values reported by Igoshin et al [6].…”

Context-aware synthetic biology by controller design: Engineering the mammalian cell

“…In this design, two factors competitively catalyze the conversion of a gene regulator between an active and inactive state. (Ai) A well-studied version of this controller is implemented with a kinase and phosphatase that competitively phosphorylate and dephosphorylate a TF (Chang et al, 2013;Jones et al, 2021;Qian and Del Vecchio, 2018). This design has been shown capable of adapting output expression to various inputs, including input pulses (Chang et al, 2013) and off-target regulation and resource competition (Jones et al, 2021).…”

Modular Dynamic Biomolecular Modelling with Bond Graphs: The Unification of Stoichiometry, Thermodynamics, Kinetics and Data

“…Type II The species include currency metabolites only; these pathways dissipate energy without creating or consuming primary metabolites. Such pathways are sometimes called futile cycles; however they have an important role to play in regulating metabolite flow [57][58][59][60][61][62].…”