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Elementary Flux Mode Analysis Revealed Cyclization Pathway as a Powerful Way for NADPH Regeneration of Central Carbon Metabolism

NADPH regeneration capacity is attracting growing research attention due to its important role in resisting oxidative stress. Besides, NADPH availability has been regarded as a limiting factor in production of industrially valuable compounds. The central carbon metabolism carries the carbon skeleton...

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Autores principales: Rui, Bin, Yi, Yin, Shen, Tie, Zheng, Meijuan, Zhou, Wenwei, Du, Honglin, Fan, Yadong, Wang, Yongkang, Zhang, Zhengdong, Xu, Shengsheng, Liu, Zhijie, Wen, Han, Xie, Xiaoyao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472234/
https://www.ncbi.nlm.nih.gov/pubmed/26086807
http://dx.doi.org/10.1371/journal.pone.0129837
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author Rui, Bin
Yi, Yin
Shen, Tie
Zheng, Meijuan
Zhou, Wenwei
Du, Honglin
Fan, Yadong
Wang, Yongkang
Zhang, Zhengdong
Xu, Shengsheng
Liu, Zhijie
Wen, Han
Xie, Xiaoyao
author_facet Rui, Bin
Yi, Yin
Shen, Tie
Zheng, Meijuan
Zhou, Wenwei
Du, Honglin
Fan, Yadong
Wang, Yongkang
Zhang, Zhengdong
Xu, Shengsheng
Liu, Zhijie
Wen, Han
Xie, Xiaoyao
author_sort Rui, Bin
collection PubMed
description NADPH regeneration capacity is attracting growing research attention due to its important role in resisting oxidative stress. Besides, NADPH availability has been regarded as a limiting factor in production of industrially valuable compounds. The central carbon metabolism carries the carbon skeleton flux supporting the operation of NADPH-regenerating enzyme and offers flexibility in coping with NADPH demand for varied intracellular environment. To acquire an insightful understanding of its NADPH regeneration capacity, the elementary mode method was employed to compute all elementary flux modes (EFMs) of a network representative of central carbon metabolism. Based on the metabolic flux distributions of these modes, a cluster analysis of EFMs with high NADPH regeneration rate was conducted using the self-organizing map clustering algorithm. The clustering results were used to study the relationship between the flux of total NADPH regeneration and the flux in each NADPH producing enzyme. The results identified several reaction combinations supporting high NADPH regeneration, which are proven to be feasible in cells via thermodynamic analysis and coincident with a great deal of previous experimental report. Meanwhile, the reaction combinations showed some common characteristics: there were one or two decarboxylation oxidation reactions in the combinations that produced NADPH and the combination constitution included certain gluconeogenesis pathways. These findings suggested cyclization pathways as a powerful way for NADPH regeneration capacity of bacterial central carbon metabolism.
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spelling pubmed-44722342015-06-29 Elementary Flux Mode Analysis Revealed Cyclization Pathway as a Powerful Way for NADPH Regeneration of Central Carbon Metabolism Rui, Bin Yi, Yin Shen, Tie Zheng, Meijuan Zhou, Wenwei Du, Honglin Fan, Yadong Wang, Yongkang Zhang, Zhengdong Xu, Shengsheng Liu, Zhijie Wen, Han Xie, Xiaoyao PLoS One Research Article NADPH regeneration capacity is attracting growing research attention due to its important role in resisting oxidative stress. Besides, NADPH availability has been regarded as a limiting factor in production of industrially valuable compounds. The central carbon metabolism carries the carbon skeleton flux supporting the operation of NADPH-regenerating enzyme and offers flexibility in coping with NADPH demand for varied intracellular environment. To acquire an insightful understanding of its NADPH regeneration capacity, the elementary mode method was employed to compute all elementary flux modes (EFMs) of a network representative of central carbon metabolism. Based on the metabolic flux distributions of these modes, a cluster analysis of EFMs with high NADPH regeneration rate was conducted using the self-organizing map clustering algorithm. The clustering results were used to study the relationship between the flux of total NADPH regeneration and the flux in each NADPH producing enzyme. The results identified several reaction combinations supporting high NADPH regeneration, which are proven to be feasible in cells via thermodynamic analysis and coincident with a great deal of previous experimental report. Meanwhile, the reaction combinations showed some common characteristics: there were one or two decarboxylation oxidation reactions in the combinations that produced NADPH and the combination constitution included certain gluconeogenesis pathways. These findings suggested cyclization pathways as a powerful way for NADPH regeneration capacity of bacterial central carbon metabolism. Public Library of Science 2015-06-18 /pmc/articles/PMC4472234/ /pubmed/26086807 http://dx.doi.org/10.1371/journal.pone.0129837 Text en © 2015 Rui et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Rui, Bin
Yi, Yin
Shen, Tie
Zheng, Meijuan
Zhou, Wenwei
Du, Honglin
Fan, Yadong
Wang, Yongkang
Zhang, Zhengdong
Xu, Shengsheng
Liu, Zhijie
Wen, Han
Xie, Xiaoyao
Elementary Flux Mode Analysis Revealed Cyclization Pathway as a Powerful Way for NADPH Regeneration of Central Carbon Metabolism
title Elementary Flux Mode Analysis Revealed Cyclization Pathway as a Powerful Way for NADPH Regeneration of Central Carbon Metabolism
title_full Elementary Flux Mode Analysis Revealed Cyclization Pathway as a Powerful Way for NADPH Regeneration of Central Carbon Metabolism
title_fullStr Elementary Flux Mode Analysis Revealed Cyclization Pathway as a Powerful Way for NADPH Regeneration of Central Carbon Metabolism
title_full_unstemmed Elementary Flux Mode Analysis Revealed Cyclization Pathway as a Powerful Way for NADPH Regeneration of Central Carbon Metabolism
title_short Elementary Flux Mode Analysis Revealed Cyclization Pathway as a Powerful Way for NADPH Regeneration of Central Carbon Metabolism
title_sort elementary flux mode analysis revealed cyclization pathway as a powerful way for nadph regeneration of central carbon metabolism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472234/
https://www.ncbi.nlm.nih.gov/pubmed/26086807
http://dx.doi.org/10.1371/journal.pone.0129837
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