title: Prediction of kinetic parameters from DNA-binding site sequences for modeling global transcription dynamics in Escherichia coli.
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, fructose 1,6-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.
authors.affiliation: Institute of Biochemical Engineering, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Hardiman
authors.forename: Hannes
authors.initials: H
authors.lastname: Meinhold
authors.forename: Johannes
authors.initials: J
authors.lastname: Hofmann
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Ewald
authors.forename: Martin
authors.initials: M
authors.lastname: Siemann-Herzberg
authors.forename: Matthias
authors.initials: M
authors.lastname: Reuss
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; D012313:RNA; D012321:DNA-Directed RNA Polymerases; D005947:Glucose