An integrated network approach identifies the isobutanol response network of Escherichia coli

Abstract Isobutanol has emerged as a potential biofuel due to recent metabolic engineering efforts. Here we used gene expression and transcription network connectivity data, genetic knockouts, and network component analysis (NCA) to map the initial isobutanol response network of Escherichia coli und...

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Main Authors: Mark P Brynildsen, James C Liao
Format: Article
Language:English
Published: Springer Nature 2009-06-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.1038/msb.2009.34
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author Mark P Brynildsen
James C Liao
author_facet Mark P Brynildsen
James C Liao
author_sort Mark P Brynildsen
collection DOAJ
description Abstract Isobutanol has emerged as a potential biofuel due to recent metabolic engineering efforts. Here we used gene expression and transcription network connectivity data, genetic knockouts, and network component analysis (NCA) to map the initial isobutanol response network of Escherichia coli under aerobic conditions. NCA revealed profound perturbations to respiration. Further investigation showed ArcA as an important mediator of this response. Quinone/quinol malfunction was postulated to activate ArcA, Fur, and PhoB in this study. In support of this hypothesis, quinone‐linked ArcA and Fur target expressions were significantly less perturbed by isobutanol under fermentative growth whereas quinol‐linked PhoB target expressions remained activated, and isobutanol impeded growth on glycerol, which requires quinones, more than on glucose. In addition, ethanol, n‐butanol, and isobutanol response networks were compared. n‐Butanol and isobutanol responses were qualitatively similar, whereas ethanol had notable induction differences of pspABCDE and ndh, whose gene products manage proton motive force. The network described here could aid design and comprehension of alcohol tolerance, whereas the approach provides a general framework to characterize complex phenomena at the systems level.
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spelling doaj-art-3a7daa436bd3468da1a622439b76e9dc2025-08-24T11:59:02ZengSpringer NatureMolecular Systems Biology1744-42922009-06-015111310.1038/msb.2009.34An integrated network approach identifies the isobutanol response network of Escherichia coliMark P Brynildsen0James C Liao1Department of Chemical and Biomolecular Engineering, University of CaliforniaDepartment of Chemical and Biomolecular Engineering, University of CaliforniaAbstract Isobutanol has emerged as a potential biofuel due to recent metabolic engineering efforts. Here we used gene expression and transcription network connectivity data, genetic knockouts, and network component analysis (NCA) to map the initial isobutanol response network of Escherichia coli under aerobic conditions. NCA revealed profound perturbations to respiration. Further investigation showed ArcA as an important mediator of this response. Quinone/quinol malfunction was postulated to activate ArcA, Fur, and PhoB in this study. In support of this hypothesis, quinone‐linked ArcA and Fur target expressions were significantly less perturbed by isobutanol under fermentative growth whereas quinol‐linked PhoB target expressions remained activated, and isobutanol impeded growth on glycerol, which requires quinones, more than on glucose. In addition, ethanol, n‐butanol, and isobutanol response networks were compared. n‐Butanol and isobutanol responses were qualitatively similar, whereas ethanol had notable induction differences of pspABCDE and ndh, whose gene products manage proton motive force. The network described here could aid design and comprehension of alcohol tolerance, whereas the approach provides a general framework to characterize complex phenomena at the systems level.https://doi.org/10.1038/msb.2009.34biofuelnetwork component analysisquinonerespirationtranscriptional regulation
spellingShingle Mark P Brynildsen
James C Liao
An integrated network approach identifies the isobutanol response network of Escherichia coli
Molecular Systems Biology
biofuel
network component analysis
quinone
respiration
transcriptional regulation
title An integrated network approach identifies the isobutanol response network of Escherichia coli
title_full An integrated network approach identifies the isobutanol response network of Escherichia coli
title_fullStr An integrated network approach identifies the isobutanol response network of Escherichia coli
title_full_unstemmed An integrated network approach identifies the isobutanol response network of Escherichia coli
title_short An integrated network approach identifies the isobutanol response network of Escherichia coli
title_sort integrated network approach identifies the isobutanol response network of escherichia coli
topic biofuel
network component analysis
quinone
respiration
transcriptional regulation
url https://doi.org/10.1038/msb.2009.34
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