4.3 Article

Exacting predictions by cybernetic model confirmed experimentally: Steady state multiplicity in the chemostat

Journal

BIOTECHNOLOGY PROGRESS
Volume 28, Issue 5, Pages 1160-1166

Publisher

WILEY-BLACKWELL
DOI: 10.1002/btpr.1583

Keywords

cybernetic mechanism; multiplicity; chemostat; Escherichia coli; metabolic regulation

Funding

  1. Dean's Research Office, Purdue University
  2. Department of Biotechnology, Ministry of Science & Technology of the Government of India
  3. Center for Science of Information (CSoI), an NSF Science and Technology Center [CCF-0939370]

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We demonstrate strong experimental support for the cybernetic model based on maximizing carbon uptake rate in describing the microorganism's regulatory behavior by verifying exacting predictions of steady state multiplicity in a chemostat. Experiments with a feed mixture of glucose and pyruvate show multiple steady state behavior as predicted by the cybernetic model. When multiplicity occurs at a dilution (growth) rate, it results in hysteretic behavior following switches in dilution rate from above and below. This phenomenon is caused by transient paths leading to different steady states through dynamic maximization of the carbon uptake rate. Thus steady state multiplicity is a manifestation of the nonlinearity arising from cybernetic mechanisms rather than of the nonlinear kinetics. The predicted metabolic multiplicity would extend to intracellular states such as enzyme levels and fluxes to be verified in future experiments. (c) 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012

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