Single-cell zeroth-order protein degradation enhances the robustness of synthetic oscillator

Mol Syst Biol. 2007:3:130. doi: 10.1038/msb4100172. Epub 2007 Jul 31.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Biological Clocks*
  • Escherichia coli / cytology*
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / metabolism*
  • Genes, Synthetic / genetics*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Kinetics
  • Models, Biological
  • Molecular Sequence Data
  • Peptide Hydrolases / metabolism
  • Protein Processing, Post-Translational*
  • RNA, Bacterial / chemistry
  • RNA, Bacterial / metabolism

Substances

  • Escherichia coli Proteins
  • RNA, Bacterial
  • tmRNA
  • Green Fluorescent Proteins
  • Peptide Hydrolases