Molecular Systems Biology
Springer Science and Business Media LLC
Single-cell zeroth-order protein degradation enhances the robustness of synthetic oscillator
Volume: 3
DOI 10.1038/msb4100172




In Escherichia coli, protein degradation in synthetic circuits is commonly achieved by the ssrA-tagged degradation system. In this work, we show that the degradation kinetics for the green fluorescent protein fused with the native ssrA tag in each cell exhibits the zeroth-order limit of the Michaelis–Menten kinetics, rather than the commonly assumed first-order. When measured in a population, the wide distribution of protein levels in the cells distorts the true kinetics and results in a first-order protein degradation kinetics as a population average. Using the synthetic gene-metabolic oscillator constructed previously, we demonstrated theoretically that the zeroth-order kinetics significantly enlarges the parameter space for oscillation and thus enhances the robustness of the design under parametric uncertainty.

Keywords zeroth-order protein degradation enhances the robustness of synthetic oscillator&author=&keyword=population heterogeneity,protein degradation,single-cell measurements,synthetic biological circuits,&subject=General Biochemistry, Genetics and Molecular Biology,Computational Theory and Mathematics,General Immunology and Microbiology,Applied Mathematics,General Agricultural and Biological Sciences,Information Systems,