Biocatalysts and Bioreactor Design

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

  1. Jin Il Kim1,†,
  2. Hyun-Seob Song1,
  3. Sunil R. Sunkara2,
  4. Arvind Lali2,
  5. Doraiswami Ramkrishna1,*

Article first published online: 16 JUL 2012

DOI: 10.1002/btpr.1583

Issue

Biotechnology Progress

Biotechnology Progress

Volume 28, Issue 5, pages 1160–1166, September/October 2012

Additional Information

How to Cite

Kim, J. I., Song, H.-S., Sunkara, S. R., Lali, A. and Ramkrishna, D. (2012), Exacting predictions by cybernetic model confirmed experimentally: Steady state multiplicity in the chemostat. Biotechnol Progress, 28: 1160–1166. doi: 10.1002/btpr.1583

Author Information

  1. 1

    School of Chemical Engineering, Purdue University, West Lafayette, IN 47907

  2. 2

    DBT-ICT-Centre for Energy Biosciences, Institute of Chemical Technology, Nathalal Parikh Marg, Matunga, Mumbai 400 019, India

  1. †

    Samsung Engineering Co., Ltd., 467-14 Samsung SEI Tower, Dogok 2 Dong, Gangnam-Gu, Seoul 135-856, Republic of Korea

*Forney Hall of Chemical Engineering, 480 Stadium Mall Drive, West Lafayette, IN 47907-2100

Publication History

  1. Issue published online: 10 OCT 2012
  2. Article first published online: 16 JUL 2012
  3. Accepted manuscript online: 26 JUN 2012 10:54PM EST
  4. Manuscript Revised: 1 JUN 2012
  5. Manuscript Received: 19 APR 2012

Funded by

  • Dean's Research Office, Purdue University
  • Department of Biotechnology, Ministry of Science & Technology of the Government of India
  • Center for Science of Information (CSoI)
  • NSF Science and Technology Center. Grant Number: CCF-0939370

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Keywords:

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

Abstract

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. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012

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