A quantitative lens on anaerobic life: leveraging the state-of-the-art fluxomics approach to explore clostridial metabolism

Wu, Chao; Cano, Melissa; Gao, Xiang; Lo, Jonathan; Maness, PinChing; Xiong, Wei

doi:10.1016/j.copbio.2019.09.012

Title: A quantitative lens on anaerobic life: leveraging the state-of-the-art fluxomics approach to explore clostridial metabolism

Abstract

Quantitative understanding of clostridial metabolism is of longstanding interest due to the importance of Clostridia as model anaerobes, biotechnology workhorses, and contributors to evolutionary history and ecosystem. Current computational methods such as flux balance analysis-based construction of clostridial metabolism in genome scale provide a fundamental framework for metabolic analysis. However, this method alone is inadequate to characterize cellular metabolic activity. Experiment-driven approaches including isotope tracer-based fluxomics in association with genetic and biochemical methods are needed to gain a more comprehensive understanding. Here we focus on typical examples where these integrated approaches have contributed to the identification of new metabolic pathways and quantification of metabolic fluxes in Clostridia. Here, we also highlight the opportunities and challenges of cutting-edge fluxomics approaches such as machine learning modeling, deuterium tracer approach, and high throughput flux phenotyping in exploring clostridial metabolism with respect to inorganic carbon utilization, redox cofactor interconversion, and other key metabolic features.

Authors:

Wu, Chao ^[1];

^[2]; Gao, Xiang ^[1]; Lo, Jonathan ^[1]; Maness, PinChing ^[1]; Xiong, Wei ^[1]

National Renewable Energy Lab. (NREL), Golden, CO (United States)
Colorado School of Mines, Golden, CO (United States)

Publication Date:: 2019-10-23

Research Org.:: National Renewable Energy Lab. (NREL), Golden, CO (United States)

Sponsoring Org.:: USDOE Office of Energy Efficiency and Renewable Energy (EERE), Sustainable Transportation Office. Bioenergy Technologies Office; USDOE National Renewable Energy Laboratory (NREL), Laboratory Directed Research and Development (LDRD) Program

OSTI Identifier:: 1573196

Alternate Identifier(s):: OSTI ID: 1706176

Report Number(s):: NREL/JA-2700-74431
Journal ID: ISSN 0958-1669

Grant/Contract Number:: AC36-08GO28308; 34715

Resource Type:: Accepted Manuscript

Journal Name:: Current Opinion in Biotechnology

Additional Journal Information:: Journal Volume: 64; Journal Issue: C; Journal ID: ISSN 0958-1669

Publisher:: Elsevier

Country of Publication:: United States

Language:: English

Subject:: 09 BIOMASS FUELS; 59 BASIC BIOLOGICAL SCIENCES; Clostridium; fluxomics; metabolic analysis; systems microbiology

Citation Formats


                    Wu, Chao, Cano, Melissa, Gao, Xiang, Lo, Jonathan, Maness, PinChing, and Xiong, Wei. A quantitative lens on anaerobic life: leveraging the state-of-the-art fluxomics approach to explore clostridial metabolism.  United States: N. p., 2019. 
Web.  doi:10.1016/j.copbio.2019.09.012.

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                    Wu, Chao, Cano, Melissa, Gao, Xiang, Lo, Jonathan, Maness, PinChing, & Xiong, Wei. A quantitative lens on anaerobic life: leveraging the state-of-the-art fluxomics approach to explore clostridial metabolism.  United States.  https://doi.org/10.1016/j.copbio.2019.09.012

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                    Wu, Chao, Cano, Melissa, Gao, Xiang, Lo, Jonathan, Maness, PinChing, and Xiong, Wei. Wed .  
"A quantitative lens on anaerobic life: leveraging the state-of-the-art fluxomics approach to explore clostridial metabolism".  United States.  https://doi.org/10.1016/j.copbio.2019.09.012.  https://www.osti.gov/servlets/purl/1573196.

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@article{osti_1573196,

  title        = {A quantitative lens on anaerobic life: leveraging the state-of-the-art fluxomics approach to explore clostridial metabolism},

  author       = {Wu, Chao and Cano, Melissa and Gao, Xiang and Lo, Jonathan and Maness, PinChing and Xiong, Wei},

  abstractNote = {Quantitative understanding of clostridial metabolism is of longstanding interest due to the importance of Clostridia as model anaerobes, biotechnology workhorses, and contributors to evolutionary history and ecosystem. Current computational methods such as flux balance analysis-based construction of clostridial metabolism in genome scale provide a fundamental framework for metabolic analysis. However, this method alone is inadequate to characterize cellular metabolic activity. Experiment-driven approaches including isotope tracer-based fluxomics in association with genetic and biochemical methods are needed to gain a more comprehensive understanding. Here we focus on typical examples where these integrated approaches have contributed to the identification of new metabolic pathways and quantification of metabolic fluxes in Clostridia. Here, we also highlight the opportunities and challenges of cutting-edge fluxomics approaches such as machine learning modeling, deuterium tracer approach, and high throughput flux phenotyping in exploring clostridial metabolism with respect to inorganic carbon utilization, redox cofactor interconversion, and other key metabolic features.},

  doi          = {10.1016/j.copbio.2019.09.012},

  journal      = {Current Opinion in Biotechnology},

  number       = C,

  volume       = 64,

  place        = {United States},

  year         = {2019},

  month        = {10}

}

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Figures / Tables:

Figure 1: Featured carbon and energetics pathways in clostridial central metabolism. Abbreviations: DHAP, dihydroxyacetone; E4P, erythrose-4-phosphate; ETF, oxidized electron-transfer flavoprotein; ETFH, reduced electron-transfer flavoprotein; F6P, fructose-6-phosphate; Fdh, formate dehydrogenase; Fd_ox, oxidized ferredoxin; Fd_red, reduced ferredoxin; GAP, glyceraldehyde-3-phosphate; Hyt, NADP-and ferredoxin-dependent hydrogenase; Nfn, NADH-dependent reduced ferredoxin: NADP oxidoreductase; PFOR, pyruvate: ferredoxinmore »

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