Understanding flux in plant metabolic networks

Current Opinion in Plant Biology

Volumn 7, Issue 3, 2004, Pages 309-317

  Schwender, Jörg ^a   Ohlrogge, John ^a   Shachar Hill, Yair ^a  

^a MICHIGAN STATE UNIVERSITY   (United States)

Author keywords

G6PDH; gas chromatography; GC; glucose 6 phosphate dehydrogenase; mass spectrometry; metabolic flux analysis; MFA; MS; NMR; nuclear magnetic resonance; OAA; OPPP; oxaloacetate; oxidative pentose phosphate pathway; PEP; phosphoenolpyruvate; TAG; TCA; triacylglycerol

Indexed keywords

CARBON;

COMPUTER PROGRAM; CORYNEBACTERIUM; CULTURE TECHNIQUE; GENETIC ENGINEERING; GENETICS; ISOTOPE LABELING; METABOLISM; METHODOLOGY; PLANT; RAPESEED; REVIEW;

BRASSICA NAPUS; CARBON; CORYNEBACTERIUM; CULTURE TECHNIQUES; GENETIC ENGINEERING; ISOTOPE LABELING; PLANTS; SOFTWARE;

EID: 2442549780     PISSN: 13695266     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.pbi.2004.03.016     Document Type: Review

References (45)

1. Sweetlove L.J., Last R.L., Fernie A.R. Predictive metabolic engineering: a goal for systems biology. Plant Physiol. 132:2003;420-425
2. Girke T., Ozkan M., Carter D., Raikhel N.V. Towards a modeling infrastructure for studying plant cells. Plant Physiol. 132:2003;410-414
3. Palsson B. In silico biology through 'omics'. Nature Biotechnol. 20:2002;649-650
4. 13C -MFA, transient flux analysis, kinetic modeling and metabolic control analysis for the analysis of photosynthesis, central carbon metabolism, the integration of carbon and nitrogen metabolism, secondary metabolism and one-carbon metabolism.
5. 13C -MFA in small-scale analysis and in the analysis of multiple fluxes in large networks are given, and the problems caused by the complexity of the intermediary metabolism of plants are discussed.
6. Stephanopoulos G. Metabolic fluxes and metabolic engineering. Metabol Eng. 1:1999;1-11
7. Stephanopoulos GN, Aristidou AA, Nielsen J: Metabolic Engineering: Principles and Methodologies. San Diego: Academic Press; 1998.
8. 13C -metabolic flux analysis Metabol Eng. 3:2001;195-206
9. 13C -NMR, MS and metabolic flux balancing in biotechnology research Q Rev Biophys. 31:1998;41-106
10. Christensen B., Nielsen J. Isotope analysis using GC/MS. Metabol Eng. 1:1999;282-290
11. Wittmann C., Heinzle E. Mass spectrometry for metabolic flux analysis. Biotechnol Bioeng. 62:1999;739-750
12. Marx A., de Graaf A.A., Wiechert W., Eggeling L., Sahm H. Determination of the fluxes in the central metabolism of Corynebacterium glutamicum by nuclear magnetic resonance spectroscopy combined with metabolite balancing. Biotechnol Bioeng. 49:1996;111-129
13. 13 -NMR spectroscopy and GC-MS Appl Microbiol Biotechnol. 47:1997;430-440
14. Petersen S., de Graaf A.A., Eggeling L., Mollney M., Wiechert W., Sahm H. In vivo quantification of parallel and bidirectional fluxes in the anaplerosis of Corynebacterium glutamicum. J Biol Chem. 275:2000;35932-35941
15. Wittmann C., Heinzle E. Application of MALDI-TOF MS to lysine-producing Corynebacterium glutamicum. A novel approach for metabolic flux analysis. Eur J Biochem. 268:2001;2441-2455
16. Petersen S., Mack C., de Graaf A.A., Riedel C., Eikmanns B.J., Sahm H. Metabolic consequences of altered phosphoenolpyruvate carboxykinase activity in Corynebacterium glutamicum reveal anaplerotic regulation mechanisms in vivo. Metabol Eng. 3:2001;344-361
17. Koffas M.A.G., Jung G.Y., Stephanopoulos G. Engineering metabolism and product formation in Corynebacterium glutamicum by coordinated gene overexpression. Metabol Eng. 5:2003;32-41
18. Hatzfeld W.D., Stitt M. A study of the rate of recycling of triose phosphates in heterotrophic Chenopodium rubrum cells, potato tubers, and maize endosperm. Planta. 180:1990;198-204
19. 13 -labelling: indications for a cytosol and a plastid-localized oxidative pentose phosphate pathway J Exp Bot. 49:1998;1917-1924
20. 13C -glucose by cell suspension of carrot (Daucus carota) measured by in vivo NMR: cycling of triose-, pentose- and hexose-phosphates Physiol Plant. 108:2000;125-133
21. Fernie A.R., Roscher A., Ratcliffe R.G., Kruger N.J. Fructose 2, 6-bisphosphate activates pyrophosphate: fructose-6-phosphate 1-phosphotransferase and increases triose phosphate to hexose phosphate cycling in heterotrophic cells. Planta. 212:2001;250-263
22. 13C ]glucose was performed during three different stages of the growth cycle of tomato cells in suspension cultures. The decrease in nutrients in the growth medium and the increases in biomass (i.e. fresh weight and dry weight) and in free cellular sugars, organic acids, protein, starch and cell wall polysaccharides were measured during culture. The labeling in sucrose, starch, glutamate and alanine (as determined by NMR) was used to derive flux ratios in central carbon metabolism. Upon the transition from exponential growth to a pre-stationary phase (which occurs via an arrest of cell division) several key fluxes (i.e. those for glycolysis and the OPPP, as well as flux through the pyruvate dehydrogenase complex) remain remarkably constant relative to the total glucose influx. In addition, futile cycles (i.e. sucrose- and triose-phosphate cycling) remained relatively unchanged and are considered to be important for the stability of the central carbon metabolism network. At the same time, fluxes into the major anabolic pathways were highly variable.
23. 14 -labeled glucose J Biol Chem. 270:1995;13147-13159
24. Dieuaide-Noubhani M., Canioni P., Raymond P. Sugar-starvation-induced changes of carbon metabolism in excised maize root tips. Plant Physiol. 115:1997;1505-1513
25. Edwards S., Nguyen B.T., Do B., Roberts J.K.M. Contribution of malic enzyme, pyruvate kinase, phosphoenolpyruvate carboxylase, and the Krebs cycle to respiration and biosynthesis and to intracellular pH regulation during hypoxia in maize root tips observed by nuclear magnetic resonance imaging and gas chromatography mass spectrometry. Plant Physiol. 116:1998;1073-1081
26. Keeling P.L., Wood J.R., Tyson R.H., Bridges I.G. Starch biosynthesis in developing wheat-grain - evidence against the direct involvement of triose phosphates in the metabolic pathway. Plant Physiol. 87:1988;311-319
27. 13 -nuclear-magnetic- resonance spectroscopy Planta. 183:1991;202-208
28. Glawischnig E., Gierl A., Tomas A., Bacher A., Eisenreich W. Retrobiosynthetic nuclear magnetic resonance analysis of amino acid biosynthesis and intermediary metabolism. Metabolic flux in developing maize kernels. Plant Physiol. 125:2001;1178-1186
29. 13C -labeled glucose and sucrose. NMR analysis of the glucosyl units of starch indicates that the cyclic metabolism of glucose by the reactions of glycolysis and the pentose phosphate pathway before incorporation into starch is extensive.
30. Schwender J., Ohlrogge J.B. Probing in vivo metabolism by stable isotope labeling of storage lipids and proteins in developing Brassica napus embryos. Plant Physiol. 130:2002;347-361 The authors establish the conditions necessary for steady-state stable-isotope labeling of developing embryos of Brassica napus. To grow embryos in culture conditions that mimicked growth in planta, the main carbon (i.e. sucrose and glucose) and nitrogen (i.e. amino acids) sources were included in the growth medium at the concentrations found in the endosperm liquid. The contribution of the different carbon sources to biomass formation during embryo culture was measured by stable-isotope labeling. Different criteria for establishing quasi metabolic and isotopic steady-states during the labeling experiment are tested and discussed. A low contribution of the OPPP to hexose breakdown was revealed by the labeling data. In addition, it was found that cytosolic acetyl-CoA is generated from TCA-cycle intermediates whereas plastidic acetyl-CoA derives mainly from glycolysis.
31. 2 ]glucose, and the labeling patterns in amino acids, lipids, sucrose and starch were measured by GC - MS and NMR. The data were used to verify a reaction network of central carbon metabolism that is distributed between the cytosol and plastid. Computer simulation of the steady-state distribution of isotopomers in intermediates of the glycolysis/OPPP network was used to fit metabolic flux parameters to the experimental data. The glycolysis/OPPP network has to be overdetermined by different labeling experiments in order to measure the key fluxes reliably.
32. Kruger N.J., von Schaewen A. The oxidative pentose phosphate pathway: structure and organization. Curr Opin Plant Biol. 6:2003;236-246
33. Follstad B.D., Stefphanopoulos G. Effect of reversible reactions on isotope label redistribution - analysis of the pentose phosphate pathway. Eur J Biochem. 252:1998;360-371
34. Roscher A., Kruger N.J., Ratcliffe R.G. Strategies for metabolic flux analysis in plants using isotope labelling. J Biotechnol. 77:2000;81-102
35. 13C -labeling Metabol Eng. 3:2001;151-162
36. 13C -MFA makes it possible to measure reversible, cyclic and parallel fluxes. Several studies in microorganisms are reviewed and reveal that different carbohydrate cycles are inherent components of the central carbon metabolism network. Current hypotheses on the physiological relevance of carbohydrate cycles are discussed.
37. Hill S.A., Ap Rees T. Fluxes of carbohydrate-metabolism in ripening bananas. Planta. 192:1994;52-60
38. Klapa M.I., Aon J.C., Stephanopoulos G. Systematic quantification of complex metabolic flux networks using stable isotopes and mass spectrometry. Eur J Biochem. 270:2003;3525-3542
39. Arauzo-Bravo M.J., Shimizu K. An improved method for statistical analysis of metabolic flux analysis using isotopomer mapping matrices with analytical expressions. J Biotechnol. 105:2003;117-133
40. Dauner M., Bailey J.E., Sauer U. Metabolic flux analysis with a comprehensive isotopomer model in Bacillus subtilis. Biotechnol Bioeng. 76:2001;144-156
41. 13C -MFA of a photosynthetic organism and the acquisition of labeling information by the use of both NMR and GC-MS for the analysis of labeled biomass.
42. Schmidt K., Carlsen M., Nielsen J., Villadsen J. Modeling isotopomer distributions in biochemical networks using isotopomer mapping matrices. Biotechnol Bioeng. 55:1997;831-840
43. Zhu T., Phalakornkule C., Ghosh S., Grossmann I.E., Koepsel R.R., Ataai M.M., Domach M.M. A metabolic network analysis and NMR experiment design tool with user interface-driven model construction for depth-first search analysis. Metabol Eng. 5:2003;74-85
44. 13C metabolic flux analysis Metabol Eng. 3:2001;265-283
45. Wiechert W., Siefke C., Degraaf A.A., Marx A. Bidirectional reaction steps in metabolic networks. 2. Flux estimation and statistical analysis. Biotechnol Bioeng. 55:1997;118-135