Single-cell zeroth-order protein degradation enhances the robustness of synthetic oscillator.
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.
Wong
Wilson W
WW
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California 90095, USA.
Tsai
Tony Y
TY
Liao
James C
JC
D000595:Amino Acid Sequence; D001683:Biological Clocks; D004926:Escherichia coli / Q000166:cytology* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005813:Genes, Synthetic / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012329:RNA, Bacterial / Q000737:chemistry / Q000378:metabolism
D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; C096222:tmRNA; D049452:Green Fluorescent Proteins; D010447:Peptide Hydrolases