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Exacting predictions by cybernetic model confirmed experimentally: Steady state multiplicity in the chemostat
Authors:Jin Il Kim  Hyun‐Seob Song  Sunil R Sunkara  Arvind Lali  Doraiswami Ramkrishna
Institution:1. School of Chemical Engineering, Purdue University, West Lafayette, IN 47907;2. DBT‐ICT‐Centre for Energy Biosciences, Institute of Chemical Technology, Nathalal Parikh Marg, Matunga, Mumbai 400 019, India
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
Keywords:cybernetic mechanism  multiplicity  chemostat  Escherichia coli  metabolic regulation
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