Abstract
A natural shift is taking place in the approaches being adopted by plant scientists in response to the accessibility of systems-based technology platforms. Metabolomics is one such field, which involves a comprehensive non-biased analysis of metabolites in a given cell at a specific time. This review briefly introduces the emerging field and a range of analytical techniques that are most useful in metabolomics when combined with computational approaches in data analyses. Using cases from Arabidopsis and other selected plant systems, this review highlights how information can be integrated from metabolomics and other functional genomics platforms to obtain a global picture of plant cellular responses. We discuss how metabolomics is enabling large-scale and parallel interrogation of cell states under different stages of development and defined environmental conditions to uncover novel interactions among various pathways. Finally, we discuss selected applications of metabolomics.



Similar content being viewed by others
References
Abe T, Kanaya S, Kinouchi M, Ichiba Y, Kozuki T, Ikemura T (2003) Informatics for unveiling hidden genome signatures. Genome Res 13:693–702
Aharoni A, Ric de Vos CH, Verhoeven HA, Maliepaard CA, Kruppa G, Bino RJ, Goodenowe DB (2002) Non-targeted metabolome analysis by use of Fourier Transform Ion Cyclotron Mass Spectrometry OMICS 6:217–234
Askenazi M, Driggers EM, Holtzman DA, Norman TC, Iverson S, Zimmer DP, Boers ME, Blomquist PR, Martinez EJ, Monreal AW, Fiebelman TP, Mayorga ME, Maxon ME, Sykes K, Tobin JV, Cordero E, Salama SR, Trueheart J, Royer JC Madden KT, Royer JC, Madden KT (2003) Integrating transcriptional and metabolite profiles to direct the engineering of lovastatin-producing fungal strains. Nature Biotechnol 21:150–156
Bajic VB, Veronika M, Veladandi PS, Meka A, Heng M-K, Rajaraman K, Pan H, Swarup S (2005) DPBE: A Text-mining Tool for Integrating Associations between Genetic and Biochemical Entities with Genome Annotation and Biochemical Terms Lists. Plant Physiol. 138 [In Press]
Baud-Camus F, Soursac MP, Davrinche M, Farinotti R (2001) Determination of N-acetylation phenotype using caffeine as a metabolic probe and high-performance liquid chromatography with either ultraviolet detection or electrospray mass spectrometry. J Chrom B Biomed Sci Appl 760:55–63
Bohmert K, Balbo I, Kopka J, Mittendorf V, Nawrath C, Poirier Y, Tischendorf G, Trethewey RN, Willmitzer L (2000) Transgenic Arabidopsis plants can accumulate polyhydroxybutyrate to up to 4% of their fresh weight. Planta 211:841–845
Brown SC, Kruppa G, Dasseux JL (2005) Metabolomics applications of FT-ICR mass spectrometry. Mass Spectrom Rev 24:223–231
Cook D, FowLer S, Fiehn O, Thomashow MF (2004) A prominent role for the CBF cold response pathway in configuring the low-temperature metabolome of Arabidopsis. Proc Natl Acad Sci USA 101:15243–15248
Cellini F, Chesson A, Colquhoun I, Constable A, Davies HV, Engel KH, Gatehouse AM, Karenlampi S, Kok EJ, Leyvay JJ, Lehesranta S, Noteburn HP, Pederson J, Smith M (2004) United effects and their detection in genetically modified crops. Food Chem Toxicol 42:1089–1125
Cooper HJ, Marshall AG (2001) Electrospray ionization Fourier transform mass spectrometric analysis of wine. J Agri Food Chem 49:5710–5718
Duran AL, Yang J, Wang L, Sumner LW (2003) Metabolomics spectral formatting, alignment and conversion tools (MSFACTs). Bioinformatics 19:2283–2293
Fiehn O, Kopka J, Dormann P, Altmann T, Trethewey RN, Willmitzer L (2000a) Metabolite profiling for plant functional genomics. Nat Biotechnol 18:1157–1161
Fiehn O, Kopaka J, Trethewey RN, Willmtizer L (2000b) Identification of uncommon plant metabolites based on calculation of elemental compositions using gas chromatography and quadrupole mass spectrometry
Fiehn O (2002) Metabolomics: The link between genotypes and phenotypes. Plant Mol Biol 48:155–171
Frick S, Kutchan TM (1999) Molecular cloning and functional expression of O-methyltransferases common to isoquinoline alkaloid and phenylpropanoid biosynthesis. Plant J 17:329–339
Fridman E, Pichersky E. (2005) Metabolomics, genomics, proteomics, and the identification of enzymes and their substrates and products. Curr Opin Plant Biol 8:242–248
Giddings G, Allison G, Brooks D, Carter A (2000) Transgenic plants as factories for biopharmaceuticals. Nature Biotechnol 18:1151–1155
Haas BJ, Wortman JR, Ronning CM, Hannick LI, Smith RK Jr, Maiti R, Chan AP, Yu C, Farzad M, Wu D, White O, Town CD (2005) Complete reannotation of the Arabidopsis genome: Methods, tools, protocols and the final release. BMC Biol 3:7
Hadacek F (2002) Secondary metabolites as plant traits: Current assessments and future perspectives. CRC Crit Rev Plant Sci 27:273–322
Hall R, Beale M, Fiehn O, Hardy N, Sumner L, Bino R (2002) Plant metabolomics: The missing link in functional genomics strategies. Plant Cell 14:1437–1440
Hirai MY, Klein M, Fujikawa Y, Yano M, Goodenowe DB, Yamazaki Y, Kanaya S, Nakamura Y, Kitayama M, Suzuki H, Sakurai N, Shibata D, Tokuhisa J, Reichelt M, Gershenzon J, Papenbrock J, Saito K (2005) Elucidation of gene-to-gene and metabolite-to-gene networks in Arabidopsis by integration of metabolomics and transcriptomics. J Biol Chem 280:25590–25595
Hirai MY, Yano M, Goodenowe DB, Kanaya S, Kimura T, Awazuhara M, Arita M, Fujiwara T, Saito K (2004) Integration of transcriptomics and metabolomics for understanding of global responses to nutritional stresses in Arabidopsis thaliana. Proc Natl Acad Sci USA 101:10205–10210
Ideker T, Thorsson V, Ranish J, Christmas R, BuhLer J (2001) Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science 292:929–934
Jansen JJ, Hoefsloot HC, Boelens HF, van der Greef J, Smilde AK (2004) Analysis of longitudinal metabolomics data. Bioinformatics 20(15):2438–2446
Jenkins H, Hardy N, Beckmann M, Draper J, Smith AR, Taylor J, Fiehn O, Goodacre R, Bino RJ, Hall R, Kopka J, Lane GA, Lange BM, Liu JR, Mendes P, Nikolau BJ, Oliver SG, Paton NW, Rhee S, Roessner-Tunali U, Saito K, Smedsgaard J, Sumner LW, Wang T, Walsh S, Wurtele ES, Kell DB (2004) A proposed framework for the description of plant metabolomics experiments and their results. Nat Biotechnol 22:1601–1606
Johnson HE, Gilbert RJ, Winson MK, Goodacre R, Simht AR, Rowland JJ, Hall MA, Kell DB (2000) Explanatory analysis of the metabolome using genetic programming of simple, interpretable rules. Genet Prog Evol Machines 1:243–258
Kant MR, Ament K, Sabelis MW, Haring MA (2004) Schuurink RC. Differential timing of spider mite-induced direct and indirect defenses in tomato plants. Plant Physiol 135:483–495
Katz JE, Dumlao DS, Clarke S, Hao J (2004) A new technique (COMSPARI) to facilitate the identification of minor compounds in complex mixtures by GC/MS and LC/MS: tools for the visualization of matched datasets. J Am Soc Mass Spectrom 15: 580–584
Kliebenstein DJ et al. (2001a) Comparative quantitative trait loci mapping of aliphatic, indolic and benzylic glucosinolate production in Arabidopsis thaliana leaves and seeds. Genetics 159:359–370
Kliebenstein DJ et al. (2001b) Genetic control of natural variation in Arabidopsis glucosinolate accumulation. Plant Physiol 126: 811–825
Kohonen T, Kaski S, Lappalainen H, Salojärvi J (1997) The adaptive-subspace self-organizing map (ASSOM). In: Proceedings of WSOM’97, Workshop on Self-Organizing Maps, Espoo, Finland, June 4–6, pp. 191–196. Helsinki University of Technology, Neural Networks Research Centre, Espoo, Finland
Krishnan P, Kruger NJ, Ratcliffe RG (2005) Metabolite fingerprinting and profiling in plants using NMR. J Exp Bot 56:255–265
Le Gall G, Colquhoun IJ, Davis AL, Collins GJ, Verhoeyen ME (2003) Metabolite profiling of tomato (Lycopersicon esculentum) using 1H NMR spectroscopy as a tool to detect potential unintended effects following a genetic modification. J Agri Food Chem 51:2447–2456
Lim EK, Li Y, Parr A, Jackson R, Ashford DA, Bowles DJ (2000) Identification of glucosyltransferase genes involved in sinapate metabolism and lignin synthesis in Arabidopsis. J Biol Chem 276:4344–4349
Lindon JC, Nicholson JK (1997) Recent advances in high-resolution NMR spectroscopic methods in bioanalytical chemistry. TRAC-Trends Anal Chem 16:190–200
Markey MK, Lo JY, Tourassi GD, Floyd CE (2003) Self-organizing map for cluster analysis of a breast cancer database. Artif Intell Med 27:113–127
Narasimhan K, Basheer C, Bajic VB, Swarup S (2003) Enhancement of plant-microbe interactions using a rhizosphere metabolomics-driven approach and its application in the removal of polychlorinated biphenyls. Plant Physiol 132:146–153
Nikiforova VJ, Kopka J, Tolstikov V, Fiehn O, Hopkins L, Hawkesford MJ, Hesse H, Hoefgen R (2005) Systems Rebalancing of Metabolism in Response to Sulfur Deprivation, as Revealed by Metabolome Analysis of Arabidopsis Plants. Plant Physiol (In press)
Noteburn HP, Lommen A, Jagt RCV, Weseman JP (2000) Chemical fingerprinting for the evaluation of unintended secondary metabolic changes in transgenic food crops. J Biotechnol 77:103–114
Ott KH, Aranibar N, Singh B, Stockton GW (2003) Metabonomics classifies pathways affected by bioactive compounds. Artificial neural network classification of NMR spectra of plant extracts. Phytochemistry 62(6):971–985
Raamsdonk LM, Teusink B, Broadhurst D, Zang N, Hayes A, Walsh MC, Berden JA, Brindle KM, Kell DB, Rowland JJ, Westerhoff HV, van Dam K, Oliver SG (2001) A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations. Nat Biotechnol 19:45–50
Sumners LW, Mendesb P, Dixona RA. (2003) Plant metabolomics: large-scale phytochemistry in the functional genomics era. Phytochemistry 62:817–836
Tesniere C, Verries C (2001) Molecular cloning and expression of cDNAs encoding alcohol dehydrogenases from Vitis vinifera L. during berry development. Plant Sci 157:77–88
Tolstikov VV, Lommen A, Nakaniski K, Tanaka N, Fiehn O (2003) Monolithical silica-based capillary reversed-phase liquid chromatography/electrospray mass spectrometery for plant metabolomics. Anal Chem 75:6737–6740
Verdonk JC, Ric de Vos CH, Verhoeven HA, Haring MA, van Tunen AJ, Schuurink RC (2003) Regulation of floral scent production in petunia revealed by targeted metabolomics. Phytochemistry 62:997–1008
Wang Y, Tang H, Nicholson JK, Hylands PJ, Sampson J, Whitcombe I, Stewart CG, Caiger S, Oru I, Holmes E (2004) Metabolomic strategy for the classification and quality control of phytomedicine: A case study of chamomile flower (Matricaria recutita L.). Planta Med 70(3):250–255
Weckwerth W, Wenzel K, Fiehn O (2004a) Process for the integrated extraction, identification and quantification of metabolites, proteins and RNA to reveal their co-regulation in biochemical networks. Proteomics 4:78–83
Weckwerth W, Loureiro ME, Wenzel K, Fiehn O (2004b) Differential metabolic networks unravel the effects of silent plant phenotypes. Proc Natl Acad Science USA 101:7809–7814
World Health Organization. (2000) Safety aspects of genetically modified foods of plant origins. In: Report of a joint FAO/WHO expert consultation on foods derived from biotechnology, held in Geneva, Switzerland, 29 May–2 June 2000. World Health Organization, Geneva, pp 1–35
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by P. P. Kumar
This special review article is dedicated to the commemoration of the retirement of Dr. Oluf L. Gamborg after 25 years of service as Founding Managing Editor of Plant Cell Reports. RB and KN have contributed equally to this review.
Rights and permissions
About this article
Cite this article
Bhalla, R., Narasimhan, K. & Swarup, S. Metabolomics and its role in understanding cellular responses in plants. Plant Cell Rep 24, 562–571 (2005). https://doi.org/10.1007/s00299-005-0054-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00299-005-0054-9