Global isotope metabolomics reveals adaptive strategies for nitrogen assimilation

Kurczy, Michael E.; Forsberg, Erica M.; Thorgersen, Michael P.; Poole, Farris L.; Benton, H. Paul; Ivanisevic, Julijana; Tran, Minerva L.; Wall, Judy D.; Elias, Dwayne A.; Adams, Michael W. W.; Siuzdak, Gary

doi:10.1021/acschembio.6b00082

Title: Global isotope metabolomics reveals adaptive strategies for nitrogen assimilation

Journal Article · Tue Apr 05 00:00:00 EDT 2016 · ACS Chemical Biology

DOI:https://doi.org/10.1021/acschembio.6b00082· OSTI ID:1326478

Kurczy, Michael E. ^[1]; Forsberg, Erica M. ^[1]; Thorgersen, Michael P. ^[2]; Poole, Farris L. ^[2]; Benton, H. Paul ^[1]; Ivanisevic, Julijana ^[3]; Tran, Minerva L. ^[1]; Wall, Judy D. ^[4]; Elias, Dwayne A. ^[5]; Adams, Michael W. W. ^[2]; Siuzdak, Gary ^[1]

The Scripps Research Institute, La Jolla, CA (United States)
Univ. of Georgia, Athens, GA (United States)
Univ. of Lausanne, Lausanne (Switzerland)
Univ. of Missouri, Columbia, MO (United States)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

Nitrogen cycling is a microbial metabolic process essential for global ecological/agricultural balance. To investigate the link between the well-established ammonium and the alternative nitrate assimilation metabolic pathways, global isotope metabolomics was employed to examine three nitrate reducing bacteria using ¹⁵NO₃ as a nitrogen source. In contrast to a control (Pseudomonas stutzeri RCH2), the results show that two of the isolates from Oak Ridge, Tennessee (Pseudomonas N2A2 and N2E2) utilize nitrate and ammonia for assimilation concurrently with differential labeling observed across multiple classes of metabolites including amino acids and nucleotides. The data reveal that the N2A2 and N2E2 strains conserve nitrogen-containing metabolites, indicating that the nitrate assimilation pathway is a conservation mechanism for the assimilation of nitrogen. Co-utilization of nitrate and ammonia is likely an adaption to manage higher levels of nitrite since the denitrification pathways utilized by the N2A2 and N2E2 strains from the Oak Ridge site are predisposed to the accumulation of the toxic nitrite. In conclusion, the use of global isotope metabolomics allowed for this adaptive strategy to be investigated, which would otherwise not have been possible to decipher.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1326478

Journal Information:: ACS Chemical Biology, Vol. 11, Issue 6; ISSN 1554-8929

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 11 works

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References (51)

Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition Goldstein, J. L.; Ho, Y. K.; Basu, S. K. Proceedings of the National Academy of Sciences, Vol. 76, Issue 1 https://doi.org/10.1073/pnas.76.1.333	journal	January 1979
Current state-of-the-art of nontargeted metabolomics based on liquid chromatography–mass spectrometry with special emphasis in clinical applications Yin, Peiyuan; Xu, Guowang Journal of Chromatography A, Vol. 1374 https://doi.org/10.1016/j.chroma.2014.11.050	journal	December 2014
Global metabolite analysis of yeast: evaluation of sample preparation methods Villas-Bôas, Silas G.; Højer-Pedersen, Jesper; Åkesson, Mats Yeast, Vol. 22, Issue 14 https://doi.org/10.1002/yea.1308	journal	January 2005
Toward Global Metabolomics Analysis with Hydrophilic Interaction Liquid Chromatography–Mass Spectrometry: Improved Metabolite Identification by Retention Time Prediction Creek, Darren J.; Jankevics, Andris; Breitling, Rainer Analytical Chemistry, Vol. 83, Issue 22 https://doi.org/10.1021/ac2021823	journal	November 2011
Absolute quantitation of intracellular metabolite concentrations by an isotope ratio-based approach Bennett, Bryson D.; Yuan, Jie; Kimball, Elizabeth H. Nature Protocols, Vol. 3, Issue 8 https://doi.org/10.1038/nprot.2008.107	journal	July 2008
MetAlign: Interface-Driven, Versatile Metabolomics Tool for Hyphenated Full-Scan Mass Spectrometry Data Preprocessing Lommen, Arjen Analytical Chemistry, Vol. 81, Issue 8 https://doi.org/10.1021/ac900036d	journal	March 2009
XCMS: Processing Mass Spectrometry Data for Metabolite Profiling Using Nonlinear Peak Alignment, Matching, and Identification Smith, Colin A.; Want, Elizabeth J.; O'Maille, Grace Analytical Chemistry, Vol. 78, Issue 3 https://doi.org/10.1021/ac051437y	journal	February 2006
The Evolution and Future of Earth’s Nitrogen Cycle Canfield, Donald E.; Glazer, Alexander N.; Falkowski, Paul G. Science, Vol. 330, Issue 6001 https://doi.org/10.1126/science.1186120	journal	October 2010
Interactive XCMS Online: Simplifying Advanced Metabolomic Data Processing and Subsequent Statistical Analyses Gowda, Harsha; Ivanisevic, Julijana; Johnson, Caroline H. Analytical Chemistry, Vol. 86, Issue 14 https://doi.org/10.1021/ac500734c	journal	June 2014
Noninvasive Urinary Metabonomic Diagnosis of Human Bladder Cancer Pasikanti, Kishore Kumar; Esuvaranathan, Kesavan; Ho, Paul C. Journal of Proteome Research, Vol. 9, Issue 6 https://doi.org/10.1021/pr901173v	journal	April 2010
Functional, biochemical and genetic diversity of prokaryotic nitrate reductases Richardson*, D. J.; Berks, B. C.; Russell, D. A. Cellular and Molecular Life Sciences, Vol. 58, Issue 2 https://doi.org/10.1007/PL00000845	journal	February 2001
Cultural eutrophication of shallow coastal waters: Coupling changing anthropogenic nutrient inputs to regional management approaches Paerl, Hans W. Limnologica, Vol. 29, Issue 3 https://doi.org/10.1016/S0075-9511(99)80009-7	journal	July 1999
Contribution of Nitrate Assimilation to the Fitness of Pseudomonas syringae pv. syringae B728a on Plants Parangan-Smith, Audrey; Lindow, Steven Applied and Environmental Microbiology, Vol. 79, Issue 2 https://doi.org/10.1128/AEM.02511-12	journal	January 2013
MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data Pluskal, Tomáš; Castillo, Sandra; Villar-Briones, Alejandro BMC Bioinformatics, Vol. 11, Issue 1 https://doi.org/10.1186/1471-2105-11-395	journal	July 2010
Determining conserved metabolic biomarkers from a million database queries Kurczy, Michael E.; Ivanisevic, Julijana; Johnson, Caroline H. Bioinformatics https://doi.org/10.1093/bioinformatics/btv475	journal	August 2015
Metabolite identification via the Madison Metabolomics Consortium Database Cui, Qiu; Lewis, Ian A.; Hegeman, Adrian D. Nature Biotechnology, Vol. 26, Issue 2 https://doi.org/10.1038/nbt0208-162	journal	February 2008
Kinetic flux profiling for quantitation of cellular metabolic fluxes Yuan, Jie; Bennett, Bryson D.; Rabinowitz, Joshua D. Nature Protocols, Vol. 3, Issue 8 https://doi.org/10.1038/nprot.2008.131	journal	July 2008
How Pseudomonas aeruginosa adapts to various environments: a metabolomic approach: Metabolic adaptation of Pseudomonas aeruginosa Frimmersdorf, Eliane; Horatzek, Sonja; Pelnikevich, Anya Environmental Microbiology, Vol. 12, Issue 6 https://doi.org/10.1111/j.1462-2920.2010.02253.x	journal	February 2010
Regulation of Carbon and Nitrogen Utilization by CbrAB and NtrBC Two-Component Systems in Pseudomonas aeruginosa Li, Wei; Lu, Chung-Dar Journal of Bacteriology, Vol. 189, Issue 15 https://doi.org/10.1128/JB.00432-07	journal	August 2007
Pattern recognition and biomarker validation using quantitative ¹ H-NMR-based metabolomics Serkova, Natalie J.; Niemann, Claus U. Expert Review of Molecular Diagnostics, Vol. 6, Issue 5 https://doi.org/10.1586/14737159.6.5.717	journal	September 2006
Kinetic flux profiling of nitrogen assimilation in Escherichia coli Yuan, Jie; Fowler, William U.; Kimball, Elizabeth Nature Chemical Biology, Vol. 2, Issue 10 https://doi.org/10.1038/nchembio816	journal	August 2006
Pathways of Pyrimidine Salvage in Pseudomonas and Former Pseudomonas: Detection of Recycling Enzymes Using High-Performance Liquid Chromatography Beck, Debrah A.; O’Donovan, Gerard A. Current Microbiology, Vol. 56, Issue 2 https://doi.org/10.1007/s00284-007-9050-3	journal	October 2007
Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis Locasale, Jason W.; Grassian, Alexandra R.; Melman, Tamar Nature Genetics, Vol. 43, Issue 9 https://doi.org/10.1038/ng.890	journal	July 2011
X ¹³ CMS: Global Tracking of Isotopic Labels in Untargeted Metabolomics Huang, Xiaojing; Chen, Ying-Jr; Cho, Kevin Analytical Chemistry, Vol. 86, Issue 3 https://doi.org/10.1021/ac403384n	journal	January 2014
Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites Wikoff, W. R.; Anfora, A. T.; Liu, J. Proceedings of the National Academy of Sciences, Vol. 106, Issue 10 https://doi.org/10.1073/pnas.0812874106	journal	February 2009
Metabolomic Analysis and Visualization Engine for LC−MS Data Melamud, Eugene; Vastag, Livia; Rabinowitz, Joshua D. Analytical Chemistry, Vol. 82, Issue 23 https://doi.org/10.1021/ac1021166	journal	December 2010
XCMS Online: A Web-Based Platform to Process Untargeted Metabolomic Data Tautenhahn, Ralf; Patti, Gary J.; Rinehart, Duane Analytical Chemistry, Vol. 84, Issue 11 https://doi.org/10.1021/ac300698c	journal	June 2012
Pre-industrial and contemporary fluxes of nitrogen through rivers: a global assessment based on typology Green, Pamela A.; Vörösmarty, Charles J.; Meybeck, Michel Biogeochemistry, Vol. 68, Issue 1 https://doi.org/10.1023/B:BIOG.0000025742.82155.92	journal	March 2004
'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data Nicholson, J. K.; Lindon, J. C.; Holmes, E. Xenobiotica, Vol. 29, Issue 11 https://doi.org/10.1080/004982599238047	journal	January 1999
isoMETLIN: A Database for Isotope-Based Metabolomics Cho, Kevin; Mahieu, Nathaniel; Ivanisevic, Julijana Analytical Chemistry, Vol. 86, Issue 19 https://doi.org/10.1021/ac5029177	journal	September 2014
METLIN: A Metabolite Mass Spectral Database Smith, Colin A.; Maille, Grace O??; Want, Elizabeth J. Therapeutic Drug Monitoring, Vol. 27, Issue 6 https://doi.org/10.1097/01.ftd.0000179845.53213.39	journal	January 2005
Dissolved Organic Nitrogen Inputs from Wastewater Treatment Plant Effluents Increase Responses of Planktonic Metabolic Rates to Warming Vaquer-Sunyer, Raquel; Conley, Daniel J.; Muthusamy, Saraladevi Environmental Science & Technology, Vol. 49, Issue 19 https://doi.org/10.1021/acs.est.5b00674	journal	September 2015
Nitrogen control in bacteria. Merrick, M. J.; Edwards, R. A. Microbiological reviews, Vol. 59, Issue 4 https://doi.org/10.1128/MMBR.59.4.604-622.1995	journal	January 1995
Differentiating Metabolites Formed from de Novo Synthesis versus Macromolecule Decomposition Yuan, Jie; Rabinowitz, Joshua D. Journal of the American Chemical Society, Vol. 129, Issue 30 https://doi.org/10.1021/ja072997c	journal	August 2007
Evolution of Nitrate Reductase: Molecular and Structural Variations on a Common Function Stolz, John F.; Basu, Partha ChemBioChem, Vol. 3, Issue 2-3 https://doi.org/10.1002/1439-7633(20020301)3:2/3<198::AID-CBIC198>3.0.CO;2-C	journal	March 2002
Determining Roles of Accessory Genes in Denitrification by Mutant Fitness Analyses Vaccaro, Brian J.; Thorgersen, Michael P.; Lancaster, W. Andrew Applied and Environmental Microbiology, Vol. 82, Issue 1 https://doi.org/10.1128/AEM.02602-15	journal	October 2015
Comprehensive and simultaneous coverage of lipid and polar metabolites for endogenous cellular metabolomics using HILIC-TOF-MS Fei, Fan; Bowdish, Dawn M. E.; McCarry, Brian E. Analytical and Bioanalytical Chemistry, Vol. 406, Issue 15 https://doi.org/10.1007/s00216-014-7797-5	journal	April 2014
Bacterial nitrate assimilation: gene distribution and regulation Luque-Almagro, Víctor M.; Gates, Andrew J.; Moreno-Vivián, Conrado Biochemical Society Transactions, Vol. 39, Issue 6 https://doi.org/10.1042/BST20110688	journal	November 2011
Metabolite profiling for plant functional genomics Fiehn, Oliver; Kopka, Joachim; Dörmann, Peter Nature Biotechnology, Vol. 18, Issue 11 https://doi.org/10.1038/81137	journal	November 2000
Regulation of nitrate assimilation by ammonium in soils and in isolated soil microorganisms Rice, Charles W.; Tiedje, James M. Soil Biology and Biochemistry, Vol. 21, Issue 4 https://doi.org/10.1016/0038-0717(89)90135-1	journal	January 1989
The KEGG resource for deciphering the genome Kanehisa, M. Nucleic Acids Research, Vol. 32, Issue 90001 https://doi.org/10.1093/nar/gkh063	journal	January 2004
Coupled biogeochemical cycles: eutrophication and hypoxia in temperate estuaries and coastal marine ecosystems Howarth, Robert; Chan, Francis; Conley, Daniel J. Frontiers in Ecology and the Environment, Vol. 9, Issue 1 https://doi.org/10.1890/100008	journal	February 2011
Biological nitrogen fixation: rates, patterns and ecological controls in terrestrial ecosystems Vitousek, Peter M.; Menge, Duncan N. L.; Reed, Sasha C. Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 368, Issue 1621 https://doi.org/10.1098/rstb.2013.0119	journal	July 2013
MetaboAnalyst 2.0--a comprehensive server for metabolomic data analysis Xia, J.; Mandal, R.; Sinelnikov, I. V. Nucleic Acids Research, Vol. 40, Issue W1 https://doi.org/10.1093/nar/gks374	journal	May 2012
Quantitative profiling of polar primary metabolites using hydrophilic interaction ultrahigh performance liquid chromatography–tandem mass spectrometry Gika, Helen G.; Theodoridis, Georgios A.; Vrhovsek, Urska Journal of Chromatography A, Vol. 1259 https://doi.org/10.1016/j.chroma.2012.02.010	journal	October 2012
Molybdenum Availability Is Key to Nitrate Removal in Contaminated Groundwater Environments Thorgersen, Michael P.; Lancaster, W. Andrew; Vaccaro, Brian J. Applied and Environmental Microbiology, Vol. 81, Issue 15 https://doi.org/10.1128/AEM.00917-15	journal	May 2015
Global metabolomics characterization of bacteria: pre-analytical treatments and profiling Bertini, Ivano; Hu, Xiaoyu; Luchinat, Claudio Metabolomics, Vol. 10, Issue 2 https://doi.org/10.1007/s11306-013-0571-4	journal	August 2013
Phage infection of an environmentally relevant marine bacterium alters host metabolism and lysate composition Ankrah, Nana Yaw D.; May, Amanda L.; Middleton, Jesse L. The ISME Journal, Vol. 8, Issue 5 https://doi.org/10.1038/ismej.2013.216	journal	December 2013
HMDB 3.0—The Human Metabolome Database in 2013 Wishart, David S.; Jewison, Timothy; Guo, An Chi Nucleic Acids Research, Vol. 41, Issue D1 https://doi.org/10.1093/nar/gks1065	journal	November 2012
Spreading Dead Zones and Consequences for Marine Ecosystems Diaz, R. J.; Rosenberg, R. Science, Vol. 321, Issue 5891 https://doi.org/10.1126/science.1156401	journal	August 2008
Nitrogen control in bacteria Merrick, M. J.; Edwards, R. A. Microbiological Reviews, Vol. 59, Issue 4 https://doi.org/10.1128/mr.59.4.604-622.1995	journal	December 1995

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Defining and Evaluating Microbial Contributions to Metabolite Variation in Microbiome-Metabolome Association Studies Noecker, Cecilia; Chiu, Hsuan-Chao; McNally, Colin P. mSystems, Vol. 4, Issue 6 https://doi.org/10.1128/msystems.00579-19	journal	December 2019
Systems-level analysis of isotopic labeling in untargeted metabolomic data by X13CMS Llufrio, Elizabeth M.; Cho, Kevin; Patti, Gary J. Nature Protocols, Vol. 14, Issue 7 https://doi.org/10.1038/s41596-019-0167-1	journal	June 2019
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