Strategies for investigating the plant metabolic network with steady-state metabolic flux analysis: Lessons from an Arabidopsis cell culture and other systems

Journal of Experimental Botany

Volumn 63, Issue 6, 2012, Pages 2309-2323

  Kruger, N J ^a   Masakapalli, S K ^a   Ratcliffe, R G ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Arabidopsis; cell culture; heterotrophic carbon metabolism; isotope labelling; mass spectrometry; metabolic flux analysis; metabolic modelling; network analysis; nuclear magnetic resonance; primary metabolism

Indexed keywords

CARBON;

ARABIDOPSIS; BIOLOGICAL MODEL; CELL COMPARTMENTALIZATION; CELL CULTURE; CYTOLOGY; ISOTOPE LABELING; METABOLISM; PLANT; REVIEW;

ARABIDOPSIS; CARBON ISOTOPES; CELL COMPARTMENTATION; CELLS, CULTURED; ISOTOPE LABELING; METABOLIC NETWORKS AND PATHWAYS; MODELS, BIOLOGICAL; PLANTS;

ARABIDOPSIS;

EID: 84859346785     PISSN: 00220957     EISSN: 14602431     Source Type: Journal    
DOI: 10.1093/jxb/err382     Document Type: Review

References (80)

1. Allen DK, Libourel IGL, Shachar-Hill Y. 2009a. Metabolic flux analysis in plants: coping with complexity. Plant, Cell and Environment 32, 1241-1257.
2. Allen DK, Ohlrogge JB, Shachar-Hill Y. 2009b. The role of light in soybean seed filling metabolism. The Plant Journal 58, 220-234.
3. Allen DK, Ratcliffe RG. 2009. Quantification of isotope label. In: Schwender, J, ed. Plant metabolic networks. New York: Springer, 105-149.
4. Allen DK, Shachar-Hill Y, Ohlrogge JB. 2007. Compartmentspecific labeling information in 13C metabolic flux analysis of plants. Phytochemistry 68, 2197-2210. (Pubitemid 47211189)
5. Alonso AP, Dale VL, Shachar-Hill Y. 2010a. Understanding fatty acid synthesis in developing maize embryos using metabolic flux analysis. Metabolic Engineering 12, 488-497.
6. Alonso AP, Goffman FD, Ohlrogge JB, Shachar-Hill Y. 2007a. Carbon conversion efficiency and central metabolic fluxes in developing sunflower (Helianthus annuus L.) embryos. The Plant Journal 52, 296-308. (Pubitemid 47537581)
7. Alonso AP, Piasecki RJ, Wang Y, LaClair RW, Shachar-Hill Y. 2010b. Quantifying the labeling and the levels of plant cell wall precursors using ion chromatography tandem mass spectrometry. Plant Physiology 153, 915-924.
8. Alonso AP, Raymond P, Hernould M, Rondeau-Mouro C, de Graaf A, Chourey P, Lahaye M, Shachar-Hill Y, Rolin D, Dieuaide-Noubhani M. 2007b. A metabolic flux analysis to study the role of sucrose synthase in the regulation of the carbon partitioning in central metabolism in maize root tips. Metabolic Engineering 9, 419-432. (Pubitemid 350019580)
9. Alonso AP, Raymond P, Rolin D, Dieuaide-Noubhani M. 2007c. Substrate cycles in the central metabolism of maize root tips under hypoxia. Phytochemistry 68, 2222-2231. (Pubitemid 47211192)
10. Alonso AP, Val DL, Shachar-Hill Y. 2011. Central metabolic fluxes in the endosperm of developing maize seeds and their implications for metabolic engineering. Metabolic Engineering 13, 96-107.
11. Alonso AP, Vigeolas H, Raymond P, Rolin D, Dieuaide-Noubhani M. 2005. A new substrate cycle in plants. Evidence for a high glucose-phosphate-to-glucose turnover from in vivo steadystate and pulse-labeling experiments with [13C]glucose and [14C]glucose. Plant Physiology 138, 2220-2232. (Pubitemid 43733564)
12. Antoniewicz MR, Kelleher JK, Stephanopoulos G. 2006. Determination of confidence intervals of metabolic fluxes estimated from stable isotope measurements. Metabolic Engineering 8, 324-337. (Pubitemid 43903302)
13. Antoniewicz MR, Kelleher JK, Stephanopoulos G. 2007a. Accurate assessment of amino acid mass isotopomer distributions for metabolic flux analysis. Analytical Chemistry 79, 7554-7559. (Pubitemid 47610424)
14. Antoniewicz MR, Kelleher JK, Stephanopoulos G. 2007b. Elementary metabolite units (EMU): a novel framework for modelling isotopic distributions. Metabolic Engineering 9, 68-86. (Pubitemid 44960874)
15. Rees T. 1980. Contribution of metabolic pathways to respiration. In: Davies, DD, ed. The biochemistry of plants: a comprehensive treatise, Vol. 2. New York: Academic Press, 1-29.
16. Arrivault S, Guenther M, Ivakov A, Feil R, Vosloh D, van Dongen JT, Sulpice R, Stitt M. 2009. Use of reverse-phase liquid chromatography, linked to tandem mass spectrometry, to profile the Calvin cycle and other metabolic intermediates in Arabidopsis rosettes at different carbon dioxide concentrations. The Plant Journal 59, 824-839.
17. Beste DJV, Bonde B, Hawkins N, Ward JL, Beale MH, Noack S, Nö h K, Kruger NJ, Ratcliffe RG, McFadden J. 2011. 13C metabolic flux analysis identifies an unusual route for pyruvate dissimilation in mycobacteria which requires isocitrate lyase and carbon dioxide fixation. PLoS Pathogens 7, e1002091.
18. Chang YJ, Suthers PF,Maranas CD. 2008. Identification of optimal measurements sets for complete flux elucidation in metabolic flux analysis experiments. Biotechnology and Bioengineering 100, 1039-1049.
19. Choi J, Antoniewicz MR. 2011. Tandem mass spectrometry: a novel approach for metabolic flux analysis. Metabolic Engineering 13, 225-233.
20. Dauner M, Bailey JE, Sauer U. 2001. Metabolic flux analysis with a comprehensive isotopomer model in Bacillus subtilis. Biotechnology and Bioengineering 76, 144-156.
21. Dieuaide-Noubhani M, Raffard G, Canioni P, Pradet A, Raymond P. 1995. Quantification of compartmented metabolic fluxes in maize root tips using isotope distribution from 13C-or 14C-labeled glucose. Journal of Biological Chemistry 270, 13147-13159.
22. Ettenhuber C, Radykewicz T, Kofer W, Koop HU, Bacher A, Eisenreich W. 2005. Metabolic flux analysis in complex isotopolog space. Recycling of glucose in tobacco plants. Phytochemistry 66, 323-335. (Pubitemid 40169992)
23. Fernie AR, Geigenberger P, Stitt M. 2005. Flux an important, but neglected, component of functional genomics. Current Opinion in Plant Biology 8, 174-182. (Pubitemid 40323547)
24. Fernie AR, Roscher A, Ratcliffe RG, Kruger NJ. 2001. Fructose 2,6-bisphosphate activates pyrophosphate:fructose-6-phosphate 1-phosphotransferase and increases triose phosphate to hexose phosphate cycling in heterotrophic cells. Planta 212, 250-263. (Pubitemid 32139882)
25. Hartung W, Ratcliffe RG. 2002. Utilization of glycine and serine as nitrogen sources in the roots of Zea mays and Chamaegigas intrepidus. Journal of Experimental Botany 53, 2305-2314. (Pubitemid 35409478)
26. Hasunuma T, Harada K, Miyazawa SI, Kondo A, Fukusaki E, Miyake C. 2010. Metabolic turnover analysis by a combination of in vivo 13C-labelling from 13CO2 and metabolic profiling with CE-MS/MS reveals rate-limiting steps of the C3 photosynthetic pathway in Nicotiana tabacum leaves. Journal of Experimental Botany 61, 1041-1051.
27. Hay J, Schwender J. 2011. Computational analysis of storage synthesis in developing Brassica napus L. (oilseed rape) embryos: flux variability analysis in relation to 13C metabolic flux analysis. The Plant Journal 67, 513-525.
28. Heinzle E, Matsuda F, Miyagawa H, Wakasa K, Nishioka T. 2007. Estimation of metabolic fluxes, expression levels and metabolite dynamics of a secondary metabolic pathway in potato using label pulse-feeding experiments combined with kinetic network modelling and simulation. The Plant Journal 50, 176-187. (Pubitemid 46493400)
29. Huege J, Goetze J, Schwarz D, Bauwe H, Hagemann M, Kopka J. 2011. Modulation of the major paths of carbon in photorespiratory mutants of Synechocystis. PLoS One 6, e16278.
30. Junker BH, Lonien J, Heady LE, Rogers A, Schwender J. 2007. Parallel determination of enzyme activities and in vivo fluxes in Brassica napus embryos grown on organic or inorganic nitrogen source. Phytochemistry 68, 2232-2242. (Pubitemid 47211183)
31. Keeling PL, Wood JR, Tyson RH, Bridges IG. 1988. Starch biosynthesis in developing wheat grain. Evidence against the direct involvement of triose phosphates in the metabolic pathway. Plant Physiology 87, 311-319.
32. Kelly EB, McMillen DP, Buono MJ. 1990. Constructing confidence intervals using the bootstrap: an application to a multi-product cost function. Review of Economics and Statistics 72, 339-344.
33. Kleijn RJ, Geertman JMA, Nfor BK, Ras C, Schipper D, Pronk JT, Heijnen JJ, van Maris AJA, van Winden WA. 2007. Metabolic flux analysis of a glycerol-overproducing Saccharomyces cerevisiae strain based on GC-MS, LC-MS and NMR-derived 13C-labelling data. FEMS Yeast Research 7, 216-231.
34. Krueger S, Giavalisco P, Krall L, Steinhauser M-C, Bü ssis D, Usadel B, Flü gge U-I, Fernie AR, Willmitzer L, Steinhauser D. 2011. A topological map of the compartmentalized Arabidopsis thaliana leaf metabolome. PLoS One 6, e17806.
35. Kruger NJ, Huddleston JE, Le Lay P, Brown ND, Ratcliffe RG. 2007a. Network flux analysis: impact of 13C-substrates on metabolism in Arabidopsis thaliana cell suspension cultures. Phytochemistry 68, 2176-2188. (Pubitemid 47211184)
36. Kruger NJ, Le Lay P, Ratcliffe RG. 2007b. Vacuolar compartmentation complicates the steady-state analysis of glucose metabolism and forces reappraisal of sucrose cycling in plants. Phytochemistry 68, 2189-2196. (Pubitemid 47211188)
37. Kruger NJ, Ratcliffe RG. 2007. Dynamic metabolic networks: going with the flow. Phytochemistry 68, 2136-2138. (Pubitemid 47211197)
38. Kruger NJ, Ratcliffe RG. 2008. Metabolic organization in plants: a challenge for the metabolic engineer. In: Bohnert HJ, Nguyen H, Lewis NG, eds. Advances in plant biochemistry and molecular biology, Volume 1. Bioengineering and molecular biology of plant pathways. Amsterdam, The Netherlands: Elsevier, 1-27.
39. Kruger NJ, Ratcliffe RG. 2009. Insights into plant metabolic networks from steady-state metabolic flux analysis. Biochimie 91, 697-702.
40. Kruger NJ, Ratcliffe RG, Roscher A. 2003. Quantitative approaches for analysing fluxes through plant metabolic networks using NMR and stable isotope labelling. Phytochemistry Reviews 2, 17-30. (Pubitemid 39012591)
41. Libourel IGL, Gehan JP, Shachar-Hill Y. 2007. Design of substrate label for steady state flux measurements in plant systems using the metabolic network of Brassica napus embryos. Phytochemistry 68, 2211-2221. (Pubitemid 47211196)
42. Libourel IGL, Shachar-Hill Y. 2008. Metabolic flux analysis in plants: from intelligent design to rational engineering. Annual Review of Plant Biology 59, 625-650. (Pubitemid 351813045)
43. Lonien J, Schwender J. 2009. Analysis of metabolic flux phenotypes for two Arabidopsis mutants with severe impairment in seed storage lipid synthesis. Plant Physiology 151, 1617-1634.
44. Lunn JE. 2007. Compartmentation in plant metabolism. Journal of Experimental Botany 58, 35-47. (Pubitemid 46026247)
45. Luo B, Groenke K, Takors R, Wandrey C, Oldiges M. 2007. Simultaneous determination of multiple intracellular metabolites in glycolysis, pentose phosphate pathway and tricarboxylic acid cycle by liquid chromatography-mass spectrometry. Journal of Chromatography A 1147, 153-164. (Pubitemid 46466829)
46. Masakapalli SK, Le Lay P, Huddleston JE, Pollock NL, Kruger NJ, Ratcliffe RG. 2010. Subcellular flux analysis of central metabolism in a heterotrophic Arabidopsis thaliana cell suspension using steady-state stable isotope labeling. Plant Physiology 152, 602-619.
47. Namba A. 2004. Simulation studies on bootstrap empirical likelihood tests. Communications in Statistics-Simulation and Computation 33, 99-108.
48. Niklas J, Schneider K, Heinzle E. 2010. Metabolic flux analysis in eukaryotes. Current Opinion in Biotechnology 21, 63-69.
49. Noack S, Nö h K, Moch M, Oldiges M, Wiechert W. 2010. Stationary versus non-stationary 13C-MFA: a comparison using a consistent dataset. Journal of Biotechnology 154, 179-190.
50. Nöh K., Wiechert W. 2011. The benefits of being transient: isotopebased metabolic flux analysis at the short time scale. Applied Microbiology and Biotechnology, 91, 1247-1265.
51. Pracharoenwattana I, Zhou W, Keech O, Francisco PB, Udomchalothorn T, Tschoep H, Stitt M, Gibon Y, Smith SM. 2010. Arabidopsis has a cytosolic fumarase required for the massive allocation of photosynthate into fumaric acid and for rapid plant growth on high nitrogen. The Plant Journal 62, 785-795.
52. Quek LE, Wittmann C, Nielsen LK, Krö mer JO. 2009. OpenFLUX: efficient modelling software for 13C-based metabolic flux analysis. Microbial Cell Factories 8, 25.
53. Ratcliffe RG, Shachar-Hill Y. 2005. Revealing metabolic phenotypes in plants: inputs from NMR analysis. Biological Reviews 80, 27-43. (Pubitemid 40207489)
54. Ratcliffe RG, Shachar-Hill Y. 2006. Measuring multiple fluxes through plant metabolic networks. The Plant Journal 45, 490-511. (Pubitemid 43373706)
55. Rontein D, Dieuaide-Noubhani M, Dufourc EJ, Raymond P, Rolin D. 2002. The metabolic architecture of plant cells. Stability of central metabolism and flexibility of anabolic pathways during the growth cycle of tomato cells. Journal of Biological Chemistry 277, 43948-43960. (Pubitemid 36157819)
56. Roscher A, Kruger NJ, Ratcliffe RG. 2000. Strategies for metabolic flux analysis in plants using isotope labelling. Journal of Biotechnology 77, 81-102. (Pubitemid 30058372)
57. Schwender J. 2008. Metabolic flux analysis as a tool in metabolic engineering of plants. Current Opinion in Biotechnology 19, 131-137.
58. Schwender J. 2009. Isotopic steady-state flux analysis. In: Schwender, J, ed. Plant metabolic networks. New York: Springer, 245-284.
59. Schwender J, Ohlrogge J, Shachar-Hill Y. 2003. A flux model of glycolysis and the oxidative pentose phosphate pathway in developing Brassica napus embryos. Journal of Biological Chemistry 278, 29442-29453. (Pubitemid 36962323)
60. Schwender J, Ohlrogge J, Shachar-Hill Y. 2004. Understanding flux in plant metabolic networks. Current Opinion in Plant Biology 7, 309-317. (Pubitemid 38611052)
61. Schwender J, Shachar-Hill Y, Ohlrogge JB. 2006. Mitochondrial metabolism in developing embryos of Brassica napus. Journal of Biological Chemistry 281, 34040-34047. (Pubitemid 46036613)
62. Shaikh AS, Tang YJ, Mukhopadhyay A, García Martín H, Gin J, Benke PI, Keasling JD. 2009. Study of stationary phase metabolism via isotopomer analysis of amino acids from an isolated protein. Biotechnology Progress 26, 52-56.
63. Shastri AA, Morgan JA. 2007. A transient isotopic labelling methodology for 13C metabolic flux analysis of photoautrophic microorganisms. Phytochemistry 68, 2302-2312. (Pubitemid 47211185)
64. Sriram G, Fulton DB, Iyer VV, Peterson JM, Zhou R, Westgate ME, Spalding MH, Shanks JV. 2004. Quantification of compartmented metabolic fluxes in developing soybean embryos by employing biosynthetically directed fractional 13C labeling, two dimensional [13C, 1H] nuclear magnetic resonance, and comprehensive isotopomer balancing. Plant Physiology 136, 3043-3057. (Pubitemid 41102175)
65. Sriram G, Gonzá lez-Rivera O, Shanks JV. 2006. Determination of biomass composition of Catharanthus roseus hairy roots for metabolic flux analysis. Biotechnology Progress 22, 1659-1663. (Pubitemid 44912671)
66. Srour O, Young JD, Eldar YC. 2011. Fluxomers: a new approach for 13C metabolic flux analysis. BMC Systems Biology 5, 129.
67. Streb S, Egli B, Eicke S, Zeeman SC. 2009. The debate on the pathway of starch synthesis: a closer look at low-starch mutants lacking plastidial phosphoglucomutase supports the chloroplastlocalized pathway. Plant Physiology 151, 1769-1772.
68. Sweetlove LJ, Fell D, Fernie AR. 2008. Getting to grips with the plant metabolic network. Biochemical Journal 409, 27-41.
69. Sweetlove LJ, Ratcliffe RG. 2011. Flux-balance modelling of plant metabolism. Frontiers in Plant Science 2, 38.
70. Troufflard S, Roscher A, Thomasset B, Barbotin JN, Rawsthorne S, Portais JC. 2007. In vivo 13C NMR determines metabolic fluxes and steady state in linseed embryos. Phytochemistry 68, 2341-2350. (Pubitemid 47224959)
71. Turgeon R, Wolf S. 2009. Phloem transport: cellular pathways and molecular trafficking. Annual Review of Plant Biology 60, 207-221.
72. Weitzel M, Wiechert W, Nöh K. 2007. The topology of metabolic isotope labeling networks. BMC Bioinformatics 8, 315.
73. Wiechert W. 2001. 13C metabolic flux analysis. Metabolic Engineering 3, 195-206.
74. Wiechert W, Mö llney M, Petersen S, de Graaf AA. 2001. A universal framework for 13C metabolic flux analysis. Metabolic Engineering 3, 265-283. (Pubitemid 32748170)
75. Williams TCR, Miguet L, Masakapalli SK, Kruger NJ, Sweetlove LJ, Ratcliffe RG. 2008. Metabolic network fluxes in heterotrophic Arabidopsis cells: stability of the flux distribution under different oxygenation conditions. Plant Physiology 148, 704-718. (Pubitemid 352847530)
76. Williams TCR, Poolman MG, Howden AJ, Schwarzlander M, Fell DA, Ratcliffe RG, Sweetlove LJ. 2010. A genome-scale metabolic model accurately predicts fluxes in central carbon metabolism under stress conditions. Plant Physiology 154, 311-323.
77. Williams TCR, Sweetlove LJ, Ratcliffe RG. 2011. Capturing metabolite channeling in metabolic flux phenotypes. Plant Physiology 157, 981-984.
78. Young JD, Walther JL, Antoniewicz MR, Yoo H, Stephanopoulos G. 2008. An elementary metabolite unit (EMU) based method of isotopically nonstationary flux analysis. Biotechnology and Bioengineering 99, 686-699. (Pubitemid 351158266)
79. Zamboni N, Fischer E, Sauer U. 2005. FiatFlux-a software for metabolic flux analysis from 13C-glucose experiments. BMC Bioinformatics 6, 209.
80. Zupke C, Stephanopoulos G. 1994. Modeling of isotope distributions and intracellular fluxes in metabolic networks using atom mapping matrices. Biotechnology Progress 10, 489-498. (Pubitemid 2151877)