Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Rui B

PROVIDER: S-EPMC4472234 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Rui Bin B Yi Yin Y Shen Tie T Zheng Meijuan M Zhou Wenwei W Du Honglin H Fan Yadong Y Wang Yongkang Y Zhang Zhengdong Z Xu Shengsheng S Liu Zhijie Z Wen Han H Xie Xiaoyao X

PloS one 20150618 6

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 ...[more]

PMID: 26086807

Similar Datasets

Project description:BackgroundMicrobial hosts offer a number of unique advantages when used as production systems for both native and heterologous small-molecules. These advantages include high selectivity and benign environmental impact; however, a principal drawback is low yield and/or productivity, which limits economic viability. Therefore a major challenge in developing a microbial production system is to maximize formation of a specific product while sustaining cell growth. Tools to rationally reconfigure microbial metabolism for these potentially conflicting objectives remain limited. Exhaustively exploring combinations of genetic modifications is both experimentally and computationally inefficient, and can become intractable when multiple gene deletions or insertions need to be considered. Alternatively, the search for desirable gene modifications may be solved heuristically as an evolutionary optimization problem. In this study, we combine a genetic algorithm and elementary mode analysis to develop an optimization framework for evolving metabolic networks with energetically favorable pathways for production of both biomass and a compound of interest.ResultsUtilization of thermodynamically-weighted elementary modes for flux reconstruction of E. coli central metabolism revealed two clusters of EMs with respect to their Delta Gp degrees. For proof of principle testing, the algorithm was applied to ethanol and lycopene production in E. coli. The algorithm was used to optimize product formation, biomass formation, and product and biomass formation simultaneously. Predicted knockouts often matched those that have previously been implemented experimentally for improved product formation. The performance of a multi-objective genetic algorithm showed that it is better to couple the two objectives in a single objective genetic algorithm.ConclusionA computationally tractable framework is presented for the redesign of metabolic networks for maximal product formation combining elementary mode analysis (a form of convex analysis), pathway thermodynamics, and a genetic algorithm to optimize the production of two industrially-relevant products, ethanol and lycopene, from E. coli. The designed algorithm can be applied to any small-scale model of cellular metabolism theoretically utilizing any substrate and applied towards the production of any product.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets