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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| Format: | Article |
| Language: | English |
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Springer Nature
2009-06-01
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| Series: | Molecular Systems Biology |
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| 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. |
| format | Article |
| id | doaj-art-3a7daa436bd3468da1a622439b76e9dc |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2009-06-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| 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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