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.
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California 90095, USA.
Wilson W
WW
Wong
Tony Y
TY
Tsai
James C
JC
Liao
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