Design tradeoffs in a synthetic gene control circuit for metabolic networks

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

The performance of genetic control circuits for metabolism is subject to a number of tradeoffs that must be addressed at the design stage. We explore how the metabolic steady state and transient response depend on the regulatory topology and design parameters such as promoter and ribosome binding site strengths. We consider a one-to-all transcriptional control circuit for an unbranched metabolic pathway with saturable enzyme kinetics. The analysis highlights a compromise between operon and non-operon topologies in terms of robustness and design flexibility. We show that enzyme half-lives are an upper bound on the speed at which the pathway can adapt to a changing metabolic demand. We also analyze the destabilizing effect of basal enzyme expression and high regulatory sensitivity, albeit the latter reduces the steady state product bias.
Original languageEnglish
Title of host publication2012 American Control Conference (ACC)
Pages2743-2748
Number of pages6
DOIs
Publication statusPublished - 1 Jun 2012
Event2012 American Control Conference, ACC 2012 - Montreal, QC, Canada
Duration: 27 Jun 201229 Jun 2012

Conference

Conference2012 American Control Conference, ACC 2012
CountryCanada
CityMontreal, QC
Period27/06/1229/06/12

Keywords

  • biochemistry
  • biocontrol
  • biotechnology
  • cellular biophysics
  • enzymes
  • topology
  • transient response
  • design tradeoffs
  • synthetic gene control circuit
  • metabolic networks
  • metabolism
  • metabolic steady state
  • regulatory topology
  • design parameters
  • transcriptional control circuit
  • unbranched metabolic pathway
  • saturable enzyme kinetics
  • nonoperon topologies
  • operon topologies
  • enzyme half-lives
  • changing metabolic demand
  • basal enzyme expression
  • regulatory sensitivity
  • steady state product bias
  • Biochemistry
  • Steady-state
  • Mathematical model
  • Genetics
  • Kinetic theory
  • Jacobian matrices
  • Eigenvalues and eigenfunctions

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