A single phosphatase can convert a robust step response into a graded, tunable or adaptive response

Microbiology (Reading). 2013 Jul;159(Pt 7):1276-1285. doi: 10.1099/mic.0.066324-0. Epub 2013 May 23.

Abstract

Many biological signalling pathways have evolved to produce responses to environmental signals that are robust to fluctuations in protein copy number and noise. Whilst beneficial for biology, this robustness can be problematic for synthetic biologists wishing to re-engineer and subsequently tune the response of a given system. Here we show that the well-characterized EnvZ/OmpR two-component signalling system from Escherichia coli possesses one such robust step response. However, the synthetic addition of just a single component into the system, an extra independently controllable phosphatase, can change this behaviour to become graded and tunable, and even show adaptation. Our approach introduces a new design principle which can be implemented simply in engineering and redesigning fast signal transduction pathways for synthetic biology.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Outer Membrane Proteins / genetics*
  • Bacterial Outer Membrane Proteins / metabolism
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Escherichia coli / genetics
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Gene Expression Regulation, Bacterial
  • Genetic Engineering / methods*
  • Models, Biological
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism
  • Multienzyme Complexes / physiology
  • Phosphoprotein Phosphatases / genetics*
  • Phosphoprotein Phosphatases / metabolism
  • Phosphoric Monoester Hydrolases / genetics*
  • Protein Kinases / genetics*
  • Protein Kinases / metabolism
  • Signal Transduction / genetics*
  • Signal Transduction / physiology
  • Synthetic Biology / methods
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism

Substances

  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Escherichia coli Proteins
  • Multienzyme Complexes
  • Taz1 protein, E coli
  • Trans-Activators
  • osmolarity response regulator proteins
  • Protein Kinases
  • Phosphoprotein Phosphatases
  • Phosphoric Monoester Hydrolases