Apr 17, 2014

Noise propagation in synthetic gene circuits for metabolic control

ACS Synthetic Biology
Diego A OyarzúnGuy-Bart V Stan

Abstract

Dynamic control of enzyme expression can be an effective strategy to engineer robust metabolic pathways. It allows a synthetic pathway to self-regulate in response to changes in bioreactor conditions or the metabolic state of the host. The implementation of this regulatory strategy requires gene circuits that couple metabolic signals with the genetic machinery, which is known to be noisy and one of the main sources of cell-to-cell variability. One of the unexplored design aspects of these circuits is the propagation of biochemical noise between enzyme expression and pathway activity. In this article, we quantify the impact of a synthetic feedback circuit on the noise in a metabolic product in order to propose design criteria to reduce cell-to-cell variability. We consider a stochastic model of a catalytic reaction under negative feedback from the product to enzyme expression. On the basis of stochastic simulations and analysis, we show that, depending on the repression strength and promoter strength, transcriptional repression of enzyme expression can amplify or attenuate the noise in the number of product molecules. We obtain analytic estimates for the metabolic noise as a function of the model parameters and show that noise a...Continue Reading

  • References21
  • Citations15

Citations

Mentioned in this Paper

Metabolic Process, Cellular
Biochemical Pathway
Promoter
Gene Amplification Technique
Metabolic Pathway
Transcriptional Repression
Gene Amplification Abnormality
Gene Circuits
Metabolic Control

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