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A theoretical interpretation of the transient sialic acid toxicity of a nanR mutant of Escherichia coli

Chu, Dominique, Roobol, Joanne, Blomfield, Ian C. (2008) A theoretical interpretation of the transient sialic acid toxicity of a nanR mutant of Escherichia coli. Journal of Molecular Biology, 375 (3). pp. 875-889. ISSN 0022-2836. (doi:10.1016/j.jmb.2007.10.073) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided) (KAR id:22674)

Language: English

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This article reports on experimental evidence that an Escherichia coli nanR mutant shows inhibited growth in N-acetylneuraminic acid. This effect is prevented when inocula are grown in an excess of glucose, but not in an excess of glycerol. The nanATEK operon is controlled by catabolite repression, suggesting that diminished expression of the nanATEK operon in the presence of glucose explains the inocula effects. Neither double nanR-nagC nor nanR dam mutants show growth inhibition in the presence of N-acetylneuraminic acid. A theoretical model of N-acetylneuraminic acid metabolism (i.e., in particular of the nanATEK and nagBACD operons) is presented; the model suggests an interpretation of this effect as being due to transient high accumulations of GlcNAc-6P in the cell. This accumulation would lead to suppression of central metabolic functions of the cell, thus causing inhibited growth. Based on the theoretical model and experimental data, it is hypothesised that the nanATEK operon is induced in a two-step mechanism. The first step is likely to be repressor displacement by N-acetylneuraminic acid. The second stage is hypothesised to involve Dam methylation to achieve full induction.

Item Type: Article
DOI/Identification number: 10.1016/j.jmb.2007.10.073
Additional information: 1089-8638 (Electronic) Journal Article Research Support, Non-U.S. Gov't
Uncontrolled keywords: Computer Simulation Escherichia coli/*genetics/metabolism Glucose/metabolism Kinetics Models, Biological *Models, Theoretical *Mutation N-Acetylneuraminic Acid/biosynthesis/genetics/metabolism/*toxicity Operon RNA, Messenger/metabolism Repressor Proteins/*genetics/metabolism
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Dominique Chu
Date Deposited: 13 Jan 2010 12:58 UTC
Last Modified: 16 Nov 2021 10:01 UTC
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