Computational and experimental analysis of redundancy in the central metabolism of Geobacter sulfurreducens.

Previous model-based analysis of the metabolic network of Geobacter sulfurreducens suggested the existence of several redundant pathways. Here, we identified eight sets of redundant pathways that included redundancy for the assimilation of acetate, and for the conversion of pyruvate into acetyl-CoA....

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Autores principales:	Daniel Segura, Radhakrishnan Mahadevan, Katy Juárez, Derek R Lovley
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/14add9e4fb404cb6be2b46138690f7a0
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spelling	oai:doaj.org-article:14add9e4fb404cb6be2b46138690f7a02021-11-25T05:41:26ZComputational and experimental analysis of redundancy in the central metabolism of Geobacter sulfurreducens.1553-734X1553-735810.1371/journal.pcbi.0040036https://doaj.org/article/14add9e4fb404cb6be2b46138690f7a02008-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18266464/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Previous model-based analysis of the metabolic network of Geobacter sulfurreducens suggested the existence of several redundant pathways. Here, we identified eight sets of redundant pathways that included redundancy for the assimilation of acetate, and for the conversion of pyruvate into acetyl-CoA. These equivalent pathways and two other sub-optimal pathways were studied using 5 single-gene deletion mutants in those pathways for the evaluation of the predictive capacity of the model. The growth phenotypes of these mutants were studied under 12 different conditions of electron donor and acceptor availability. The comparison of the model predictions with the resulting experimental phenotypes indicated that pyruvate ferredoxin oxidoreductase is the only activity able to convert pyruvate into acetyl-CoA. However, the results and the modeling showed that the two acetate activation pathways present are not only active, but needed due to the additional role of the acetyl-CoA transferase in the TCA cycle, probably reflecting the adaptation of these bacteria to acetate utilization. In other cases, the data reconciliation suggested additional capacity constraints that were confirmed with biochemical assays. The results demonstrate the need to experimentally verify the activity of key enzymes when developing in silico models of microbial physiology based on sequence-based reconstruction of metabolic networks.Daniel SeguraRadhakrishnan MahadevanKaty JuárezDerek R LovleyPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 4, Iss 2, p e36 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Daniel Segura Radhakrishnan Mahadevan Katy Juárez Derek R Lovley Computational and experimental analysis of redundancy in the central metabolism of Geobacter sulfurreducens.
description	Previous model-based analysis of the metabolic network of Geobacter sulfurreducens suggested the existence of several redundant pathways. Here, we identified eight sets of redundant pathways that included redundancy for the assimilation of acetate, and for the conversion of pyruvate into acetyl-CoA. These equivalent pathways and two other sub-optimal pathways were studied using 5 single-gene deletion mutants in those pathways for the evaluation of the predictive capacity of the model. The growth phenotypes of these mutants were studied under 12 different conditions of electron donor and acceptor availability. The comparison of the model predictions with the resulting experimental phenotypes indicated that pyruvate ferredoxin oxidoreductase is the only activity able to convert pyruvate into acetyl-CoA. However, the results and the modeling showed that the two acetate activation pathways present are not only active, but needed due to the additional role of the acetyl-CoA transferase in the TCA cycle, probably reflecting the adaptation of these bacteria to acetate utilization. In other cases, the data reconciliation suggested additional capacity constraints that were confirmed with biochemical assays. The results demonstrate the need to experimentally verify the activity of key enzymes when developing in silico models of microbial physiology based on sequence-based reconstruction of metabolic networks.
format	article
author	Daniel Segura Radhakrishnan Mahadevan Katy Juárez Derek R Lovley
author_facet	Daniel Segura Radhakrishnan Mahadevan Katy Juárez Derek R Lovley
author_sort	Daniel Segura
title	Computational and experimental analysis of redundancy in the central metabolism of Geobacter sulfurreducens.
title_short	Computational and experimental analysis of redundancy in the central metabolism of Geobacter sulfurreducens.
title_full	Computational and experimental analysis of redundancy in the central metabolism of Geobacter sulfurreducens.
title_fullStr	Computational and experimental analysis of redundancy in the central metabolism of Geobacter sulfurreducens.
title_full_unstemmed	Computational and experimental analysis of redundancy in the central metabolism of Geobacter sulfurreducens.
title_sort	computational and experimental analysis of redundancy in the central metabolism of geobacter sulfurreducens.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/14add9e4fb404cb6be2b46138690f7a0
work_keys_str_mv	AT danielsegura computationalandexperimentalanalysisofredundancyinthecentralmetabolismofgeobactersulfurreducens AT radhakrishnanmahadevan computationalandexperimentalanalysisofredundancyinthecentralmetabolismofgeobactersulfurreducens AT katyjuarez computationalandexperimentalanalysisofredundancyinthecentralmetabolismofgeobactersulfurreducens AT derekrlovley computationalandexperimentalanalysisofredundancyinthecentralmetabolismofgeobactersulfurreducens
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Computational and experimental analysis of redundancy in the central metabolism of Geobacter sulfurreducens.

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