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Metabolomic systems biology of trypanosomes


Metabolomics analysis, which aims at the systematic identification and quantification of all metabolites in biological systems, is emerging as a powerful new tool to identify biomarkers of disease, report on cellular responses to environmental perturbation, and to identify the targets of drugs. Here we discuss recent developments in metabolomic analysis, from the perspective of trypanosome research, highlighting remaining challenges and the most promising areas for future research.

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*Corresponding author: Faculty of Biomedical and Life Sciences and Wellcome Trust Centre of Molecular Parasitology, University of Glasgow, Glasgow Biomedical Research Centre, Glasgow G12 8TA, United Kingdom. Tel: 0141-330-6904. Fax: 0141-330-4600. Email:
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Albert M. A., Haanstra J. R., Hannaert V., Van Roy J., Opperdoes F. R., Bakker B. M. and Michels P. A. (2005). Experimental and in silico analyses of glycolytic flux control in bloodstream form Trypanosoma brucei. Journal of Biological Chemistry 280, 2830628315.
Bakker B. M., Michels P. A., Opperdoes F. R. and Westerhoff H. V. (1997). Glycolysis in bloodstream form Trypanosoma brucei can be understood in terms of the kinetics of the glycolytic enzymes. Journal of Biological Chemistry 272, 32073215.
Bakker B. M., Michels P. A., Opperdoes F. R. and Westerhoff H. V. (1999 a). What controls glycolysis in bloodstream form Trypanosoma brucei? Journal of Biological Chemistry 274, 1455114559.
Bakker B. M., Walsh M. C., ter Kuile B. H., Mensonides F. I., Michels P. A., Opperdoes F. R. and Westerhoff H. V. (1999 b). Contribution of glucose transport to the control of the glycolytic flux in Trypanosoma brucei. Proceedings of the National Academy of Sciences, USA 96, 1009810103.
Barrett M. P., Burchmore R. J., Stich A., Lazzari J. O., Frasch A. C., Cazzulo J. J. and Krishna S. (2003). The trypanosomiases. Lancet 362, 14691480.
Breitling R., Ritchie S., Goodenowe D., Stewart M. L. and Barrett M. P. (2006 a). Ab initio prediction of metabolic networks using Fourier Transform Mass Spectrometry data. Metabolomics 2, 155164.
Breitling R., Pitt A. R. and Barrett M. P. (2006 b). Precision mapping of the metabolome. Trends in Biotechnology 24, 543548.
Breitling R., Vitkup D. and Barrett M. P. (2008). New surveyor tools for charting microbial metabolic maps. Nature Reviews Microbiology 6, 156161.
Bruggeman F. J. and Westerhoff H. V. (2007). The nature of systems biology. Trends in Microbiology 15, 4550.
Chavali A. K., Whittemore J. D., Eddy J. A., Williams K. T. and Papin J. A. (2008). Systems analysis of metabolism in the pathogenic trypanosomatid. Leishmania major. Molecular Systems Biology 4, 177.
Chukualim B., Peters N., Hertz-Fowler C. and Berriman M. (2008). TrypanoCyc – a metabolic pathway database for Trypanosoma brucei. BMC Bioinformatics 9 (Suppl 10), P5.
Coustou V., Besteiro S., Rivière L., Biran M., Biteau N., Franconi J. M., Boshart M., Baltz T. and Bringaud F. (2005). A mitochondrial NADH-dependent fumarate reductase involved in the production of succinate excreted by procyclic Trypanosoma brucei. Journal of Biological Chemistry 280, 1655916570.
Coustou V., Biran M., Breton M., Guegan F., Rivière L., Plazolles N., Nolan D., Barrett M. P., Franconi J. M. and Bringaud F. (2008). Glucose-induced remodeling of intermediary and energy metabolism in procyclic Trypanosoma brucei. Journal of Biological Chemistry 283, 1634216354.
Cubbon S., Antonio C., Wilson J. and Thomas-Oates J. (2009). Metabolomic applications of HILIC-LC-MS. Mass Spectrometry Reviews [Epub ahead of print]. doi:10.1002/mas.20252
Ding J., Sorensen C. M., Zhang Q., Jiang H., Jaitly N., Livesay E. A., Shen Y., Smith R. D. and Metz T. O. (2007). Capillary LC coupled with high-mass measurement accuracy mass spectrometry for metabolic profiling. Analytical Chemistry 79, 60816093.
Doyle M. A., MacRae J. I., De Souza D. P., Saunders E. C., McConville M. J. and Likić V. A. (2009). LeishCyc: a biochemical pathways database for Leishmania major. BMC Systems Biology 3, 57.
Dunn W. B., Broadhurst D., Brown M., Baker P. N., Redman C. W., Kenny L. C. and Kell D. B. (2008). Metabolic profiling of serum using Ultra Performance Liquid Chromatography and the LTQ-Orbitrap mass spectrometry system. Journal of Chromatography B Analytical Technologies for Biomedical and Life Sciences 871, 288298.
Edwards J. S., Ibarra R. U. and Palsson B. O. (2001). In silico predictions of Escherichia coli metabolic capabilities are consistent with experimental data. Nature Biotechnology 19, 125130.
Fairlamb A. H., Henderson G. B., Bacchi C. J. and Cerami A. (1987). In vivo effects of difluoromethylornithine on trypanothione and polyamine levels in bloodstream forms of Trypanosoma brucei. Molecular and Biochemical Parasitology 24, 185191.
Feist A. M., Herrgård M. J., Thiele I, Reed J. L. and Palsson B. Ø. (2009). Reconstruction of biochemical networks in microorganisms. Nature Reviews Microbiology 7, 129143.
Haanstra J. R., Stewart M., Luu V. D., van Tuijl A., Westerhoff H. V., Clayton C. and Bakker B. M. (2008 b). Control and regulation of gene expression: quantitative analysis of the expression of phosphoglycerate kinase in bloodstream form Trypanosoma brucei. Journal of Biological Chemistry 283, 24952507.
Haanstra J. R., van Tuijl A., Kessler P., Reijnders W., Michels P. A., Westerhoff H. V., Parsons M. and Bakker B. M. (2008 a). Compartmentation prevents a lethal turbo-explosion of glycolysis in trypanosomes. Proceedings of the National Academy of Sciences, USA 105, 1771817723.
Hynne F., Danø S. and Sørensen P. G. (2001). Full-scale model of glycolysis in Saccharomyces cerevisiae. Biophysical Chemistry 94, 121163.
Jamshidi N. and Palsson B.Ø. (2007). Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv using the in silico strain iNJ661 and proposing alternative drug targets. BMC Systems Biology 1, 26.
Jourdan F., Breitling R., Barrett M. P. and Gilbert D. (2008). MetaNetter: inference and visualization of high-resolution metabolomic networks. Bioinformatics 24, 143145.
Kamleh A., Barrett M. P., Wildridge D., Burchmore R. J., Scheltema R. A. and Watson D. G. (2008 a). Metabolomic profiling using Orbitrap Fourier transform mass spectrometry with hydrophilic interaction chromatography: a method with wide applicability to analysis of biomolecules. Rapid Communications in Mass Spectrometry 22, 19121918.
Kamleh M. A., Hobani Y., Dow J. A. and Watson D. G. (2008 b). Metabolomic profiling of Drosophila using liquid chromatography Fourier transform mass spectrometry. FEBS Letters 582, 29162922.
Kanehisa M., Araki M., Goto S., Hattori M., Hirakawa M., Itoh M., Katayama T., Kawashima S., Okuda S., Tokimatsu T. and Yamanishi Y (2008). KEGG for linking genomes to life and the environment. Nucleic Acids Research 36, D480D484.
Karp P. D., Paley S. and Romero P. (2002). The Pathway Tools software. Bioinformatics 18 (Suppl 1), S225S232.
Kiefer P., Portais J. C. and Vorholt J. A. (2008). Quantitative metabolome analysis using liquid chromatography-high-resolution mass spectrometry Analytical Biochemistry 382, 94–100.
Kümmel A., Panke S. and Heinemann M. (2006). Systematic assignment of thermodynamic constraints in metabolic network models. BMC Bioinformatics 7, 51.
Lim H. K., Chen J., Sensenhauser C., Cook K. and Subrahmanyam V. (2007). Metabolite identification by data-dependent accurate mass spectrometric analysis at resolving power of 60,000 in external calibration mode using an LTQ/Orbitrap. Rapid Communications in Mass Spectrometry 21, 18211832.
Mackenzie N. E., Hall J. E., Flynn I. W. and Scott A. I. (1983). 13C nuclear magnetic resonance studies of anaerobic glycolysis in Trypanosoma brucei spp. Bioscience Reports 3, 141151.
Moreno B., Urbina J. A., Oldfield E., Bailey B. N., Rodrigues C. O. and Docampo R. (2000). 31P NMR spectroscopy of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major. Evidence for high levels of condensed inorganic phosphates. Journal of Biological Chemistry 275, 2835628362.
Niittylae T., Chaudhuri B., Sauer U. and Frommer W. B. (2009). Comparison of quantitative metabolite imaging tools and carbon-13 techniques for fluxomics. Methods in Molecular Biology 553, 355372.
Rivière L., van Weelden S. W., Glass P., Vegh P., Coustou V., Biran M., van Hellemond J. J., Bringaud F., Tielens A. G. and Boshart M. (2004). Acetyl:succinate CoA-transferase in procyclic Trypanosoma brucei. Gene identification and role in carbohydrate metabolism. Journal of Biological Chemistry 279, 4533745346.
Roberts S. B., Robichaux J. L., Chavali A. K., Manque P. A., Lee V., Lara A. M., Papin J. A. and Buck G. A. (2009). Proteomic and network analysis characterize stage-specific metabolism in Trypanosoma cruzi. BMC Systems Biology 3, 52.
Robinson M. D., De Souza D. P., Keen W. W., Saunders E. C., McConville M. J., Speed T. P. and Likić V. A. (2007). A dynamic programming approach for the alignment of signal peaks in multiple gas chromatography-mass spectrometry experiments. BMC Bioinformatics 8, 419.
Rogers S., Scheltema R. A., Girolami M. and Breitling R. (2009) Probabilistic assignment of formulas to mass peaks in metabolomics experiments. Bioinformatics 25, 512518.
Scheltema R. A., Decuypere S., Dujardin J. C., Watson D., Jansen R. C. and Breitling R (2009). A simple data reduction method for high resolution LC/MS data in metabolomics. Bioanalysis 1, 15691578.
Scheltema R. A., Kamleh A, Wildridge D., Ebikeme C., Watson D. G., Barrett M. P., Jansen R. C. and Breitling R. (2008) Increasing the mass accuracy of high-resolution LC-MS data using background ions: a case study on the LTQ-Orbitrap. Proteomics 8 46474656.
Shim H. and Fairlamb A. H. (1988). Levels of polyamines, glutathione and glutathione-spermidine conjugates during growth of the insect trypanosomatid Crithidia fasciculata. Journal of General Microbiology 134, 807817.
Snoep J. L., Bruggeman F., Olivier B. G. and Westerhoff H. V. (2006). Towards building the silicon cell: a modular approach. Biosystems 83, 207216.
Suhre K. and Schmitt-Kopplin P. (2008). MassTRIX: mass translator into pathways. Nucleic Acids Research 36, W481W484.
Tang Y. J., Martin H. G., Myers S., Rodriguez S., Baidoo E. E. and Keasling J. D. (2009). Advances in analysis of microbial metabolic fluxes via (13)C isotopic labeling. Mass Spectrometry Reviews 28, 362375.
Teusink B., Passarge J., Reijenga C. A., Esgalhado E., Van der Weijden C. C., Schepper M., Walsh M. C., Bakker B. M., Van Dam K., Westerhoff H. V. and Snoep J. L. (2000). Can yeast glycolysis be understood in terms of in vitro kinetics of the constituent enzymes? Testing biochemistry. European Journal of Biochemistry 267, 53135329.
van der Werf M. J., Jellema R. H. and Hankemeier T. (2005). Microbial metabolomics: replacing trial-and-error by the unbiased selection and ranking of targets. Journal of Industrial Microbiology and Biotechnology 32, 234252.
Visser N. and Opperdoes F. R. (1980). Glycolysis in Trypanosoma brucei. European Journal of Biochemistry 103, 623632.
Wiechert W., Schweissgut O., Takanaga H. and Frommer W. B. (2007). Fluxomics: mass spectrometry versus quantitative imaging. Current Opinion in Plant Biology 10, 323330.
Xiao Y., McCloskey D. E. and Phillips M. A. (2009). RNA interference-mediated silencing of ornithine decarboxylase and spermidine synthase genes in Trypanosoma brucei provides insight into regulation of polyamine biosynthesis. Eukaryotic Cell 8, 747755.
Yang Z. (2006). Online hyphenated liquid chromatography-nuclear magnetic resonance spectroscopy-mass spectrometry for drug metabolite and nature product analysis. Journal of Pharmaceutical and Biomedical Analysis 40, 516527.
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