A dynamic model of the phosphate response system with synthetic promoters in Escherichia coli

Conference Date
2017
Location
Lyon, France
ISBN
978-0-262-34633-7
Date Published
September 2017
Conference Date: 2017, Vol. 14, Pages 412-419.
(doi: 10.7551/ecal_a_069)
© 2017 Massachusetts Institute of Technology Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license
Article PDF (1.18 MB)
Abstract

The bacteria E. coli have developed one of the most efficient regulatory response to phosphate starvation that is known in detail. Achieving a mechanistic understanding of this system, realized by Pho regulon at the genetic level, has implications for applications in artificial life and for others in biotechnology that exploit such mechanisms. To this end, we present a dynamical model of Pho regulon, coupled with a layered description of its regulation in the experimental conditions of phosphate starvation. The model describes the dynamics of two-component regulatory system together with the key regulatory promoter PhoB and experimental data on promoter PhoA. The model is parameterized according to the feasible range given in the literature, and fitted to the dynamic response of our experimental data on alkaline phosphatase production, coded as Gfp. Sensitivity analysis demonstrates that the rate of Pho transcription has a significant influence over the expression of Pho-controlled genes. Variations in the transcription rates alter the sensitivity of the phosphate starvation response to external phosphate concentration, whereas variations in the translation rates affect the gain of the system. Our model provides a dynamic description of the core determinants of Pho regulon and promoter activities and their response to the change of external phosphate level. As the model architecture is intrinsically open to integrate supplementary layers, together with experimental findings, it should provide insights in investigations on engineering new dynamic sensors and regulators for living technologies.