Analysis of a genetic-metabolic oscillator with piecewise linear models

Madalena Chaves, Diego Oyarzun, Jean-Luc Gouze

Research output: Contribution to journalArticlepeer-review

Abstract

Interactions between gene regulatory networks and metabolism produce a diversity of dynamics, including multistability and oscillations. Here, we characterize a regulatory mechanism that drives the emergence of periodic oscillations in metabolic networks subject to genetic feedback regulation by pathway intermediates. We employ a qualitative formalism based on piecewise linear models to systematically analyze the behavior of gene-regulated metabolic pathways. For a pathway with two metabolites and three enzymes, we prove the existence of two co-existing oscillatory behaviors: damped oscillations towards a fixed point or sustained oscillations along a periodic orbit. We show that this mechanism closely resembles the “metabolator”, a genetic-metabolic circuit engineered to produce autonomous oscillations in vivo.
Original languageEnglish
Pages (from-to)259-269
Number of pages11
JournalJournal of Theoretical Biology
Volume462
Early online date14 Nov 2018
DOIs
Publication statusPublished - 7 Feb 2019

Keywords

  • Metabolic pathways
  • Synthetic biology
  • Gene regulatory networks
  • Piecewise affine systems
  • Periodic orbits
  • Metabolic engineering

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