title: A single phosphatase can convert a robust step response into a graded, tunable or adaptive response.
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.
authors.affiliation: Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan, ROC.|Oxford Centre for Integrative Systems Biology, Department of Biochemistry, South Parks Road, Oxford OX1 3QU, UK.|Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.|Department of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, UK.
authors.forename: Yo-Cheng
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.|Oxford Centre for Integrative Systems Biology, Department of Biochemistry, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Judith P
authors.initials: JP
authors.lastname: Armitage
authors.affiliation: Department of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, UK.|Oxford Centre for Integrative Systems Biology, Department of Biochemistry, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Antonis
authors.initials: A
authors.lastname: Papachristodoulou
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.|Oxford Centre for Integrative Systems Biology, Department of Biochemistry, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: George H
authors.initials: GH
authors.lastname: Wadhams
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005818:Genetic Engineering / Q000379:methods*; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D058615:Synthetic Biology / Q000379:methods; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D009097:Multienzyme Complexes; C072091:Taz1 protein, E coli; D015534:Trans-Activators; C112177:osmolarity response regulator proteins; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D010744:Phosphoric Monoester Hydrolases