Abstract
The majority of dynamic gene regulatory network (GRN) models are
comprised of only a few genes and do not take multiple transcription
regulation into account. The models are conceived in this way in order
to minimize the number of kinetic parameters. In this paper, we propose
a new approach for predicting kinetic parameters from DNA-binding site
sequences by correlating the protein-DNA binding affinities with
nucleotide sequence conservation. We present the dynamic modeling of the
cra modulon transcription in Escherichia coli during glucose-limited
fed-batch cultivation. The concentration of the Cra regulator protein
inhibitor, fructose1,6-bis(phosphate), decreases sharply, eventually
leading to the repression of transcription. Total RNA concentration data
indicate a strong regulation of transcription through the availability
of RNA polymerase. A critical assessment of the results of the model
simulations supports this finding. This new approach for the prediction
of transcription dynamics may improve the metabolic engineering of gene
regulation processes. (C) 2009 Published by Elsevier Inc.
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