Integrative approaches to enhance understanding of plant metabolic pathway structure and regulation

Plant Physiology

Volumn 169, Issue 3, 2015, Pages 1499-1511

  Tohge, Takayuki ^a   Scossa, Federico ^b   Fernie, Alisdair R ^a  

^a MAX PLANCK INSTITUTE OF MOLECULAR PLANT PHYSIOLOGY   (Germany)

^b ISTITUTO NAZIONALE DELLA NUTRIZIONE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

PLANT PROTEIN;

FACTUAL DATABASE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; GENOMICS; METABOLISM; PHYSIOLOGY; PLANT; PLANT GENOME; SYSTEMS BIOLOGY;

DATABASES, FACTUAL; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, PLANT; GENOME, PLANT; GENOMICS; METABOLIC NETWORKS AND PATHWAYS; PLANT PROTEINS; PLANTS; SYSTEMS BIOLOGY;

EID: 84946219764     PISSN: 00320889     EISSN: 15322548     Source Type: Journal    
DOI: 10.1104/pp.15.01006     Document Type: Article

References (148)

1. Achnine L, Huhman DV, Farag MA, Sumner LW, Blount JW, Dixon RA (2005) Genomics-based selection and functional characterization of triterpene glycosyltransferases from the model legume Medicago truncatula. Plant J 41: 875–887
2. Aharoni A, Brandizzi F (2012) High-resolution measurements in plant biology. Plant J 70: 1–4
3. Alejandro S, Lee Y, Tohge T, Sudre D, Osorio S, Park J, Bovet L, Lee Y, Geldner N, Fernie AR, et al (2012) AtABCG29 is a monolignol transporter involved in lignin biosynthesis. Curr Biol 22: 1207–1212
4. Alseekh S, Tohge T, Wendenberg R, Scossa F, Omranian N, Li J, Kleessen S, Giavalisco P, Pleban T, Mueller-Roeber B, et al (2015) Identification and mode of inheritance of quantitative trait loci for secondary metabolite abundance in tomato. Plant Cell 27: 485–512
5. Alvarez S, Marsh EL, Schroeder SG, Schachtman DP (2008) Metabolomic and proteomic changes in the xylem sap of maize under drought. Plant Cell Environ 31: 325–340
6. Araújo WL, Ishizaki K, Nunes-Nesi A, Larson TR, Tohge T, Krahnert I, Witt S, Obata T, Schauer N, Graham IA, et al (2010) Identification of the 2-hydroxyglutarate and isovaleryl-CoA dehydrogenases as alternative electron donors linking lysine catabolism to the electron transport chain of Arabidopsis mitochondria. Plant Cell 22: 1549–1563
7. Araújo WL, Ishizaki K, Nunes-Nesi A, Tohge T, Larson TR, Krahnert I, Balbo I, Witt S, Dörmann P, Graham IA, et al (2011) Analysis of a range of catabolic mutants provides evidence that phytanoyl-coenzyme A does not act as a substrate of the electron-transfer flavoprotein/electrontransfer flavoprotein:ubiquinone oxidoreductase complex in Arabidopsis during dark-induced senescence. Plant Physiol 157: 55–69
8. Bartling D, Seedorf M, Schmidt RC, Weiler EW (1994) Molecular characterization of two cloned nitrilases from Arabidopsis thaliana: key enzymes in biosynthesis of the plant hormone indole-3-acetic acid. Proc Natl Acad Sci USA 91: 6021–6025
9. Batushansky A, Kirma M, Grillich N, Toubiana D, Pham PA, Balbo I, Fromm H, Galili G, Fernie AR, Fait A (2014) Combined transcriptomics and metabolomics of Arabidopsis thaliana seedlings exposed to exogenous GABA suggest its role in plants is predominantly metabolic. Mol Plant 7: 1065–1068
10. Bielecka M, Watanabe M, Morcuende R, Scheible WR, Hawkesford MJ, Hesse H, Hoefgen R (2014) Transcriptome and metabolome analysis of plant sulfate starvation and resupply provides novel information on transcriptional regulation of metabolism associated with sulfur, nitrogen and phosphorus nutritional responses in Arabidopsis. Front Plant Sci 5: 805
11. Bolger A, Scossa F, Bolger ME, Lanz C, Maumus F, Tohge T, Quesneville H, Alseekh S, Sørensen I, Lichtenstein G, et al (2014) The genome of the stress-tolerant wild tomato species Solanum pennellii. Nat Genet 46: 1034–1038
12. Boutanaev AM, Moses T, Zi J, Nelson DR, Mugford ST, Peters RJ, Osbourn A (2015) Investigation of terpene diversification across multiple sequenced plant genomes. Proc Natl Acad Sci USA 112: E81–E88
13. Caldana C, Degenkolbe T, Cuadros-Inostroza A, Klie S, Sulpice R, Leisse A, Steinhauser D, Fernie AR, Willmitzer L, Hannah MA (2011) Highdensity kinetic analysis of the metabolomic and transcriptomic response of Arabidopsis to eight environmental conditions. Plant J 67: 869–884
14. Carrari F, Baxter C, Usadel B, Urbanczyk-Wochniak E, Zanor MI, Nunes- Nesi A, Nikiforova V, Centero D, Ratzka A, Pauly M, et al (2006) Integrated analysis of metabolite and transcript levels reveals the metabolic shifts that underlie tomato fruit development and highlight regulatory aspects of metabolic network behavior. Plant Physiol 142: 1380–1396
15. Carreno-Quintero N, Bouwmeester HJ, Keurentjes JJB (2013) Genetic analysis of metabolome-phenotype interactions: from model to crop species. Trends Genet 29: 41–50
16. Cavalcanti JH, Esteves-Ferreira AA, Quinhones CG, Pereira-Lima IA, Nunes-Nesi A, Fernie AR, Araújo WL (2014) Evolution and functional implications of the tricarboxylic acid cycle as revealed by phylogenetic analysis. Genome Biol Evol 6: 2830–2848
17. Centeno DC, Osorio S, Nunes-Nesi A, Bertolo ALF, Carneiro RT, Araújo WL, Steinhauser MC, Michalska J, Rohrmann J, Geigenberger P, et al (2011) Malate plays a crucial role in starch metabolism, ripening, and soluble solid content of tomato fruit and affects postharvest softening. Plant Cell 23: 162–184
18. Conklin PL, Gatzek S, Wheeler GL, Dowdle J, Raymond MJ, Rolinski S, Isupov M, Littlechild JA, Smirnoff N (2006) Arabidopsis thaliana VTC4 encodes L-galactose-1-P phosphatase, a plant ascorbic acid biosynthetic enzyme. J Biol Chem 281: 15662–15670
19. Curry J, Aluru M, Mendoza M, Nevarez J, Melendrez M, O’Connell MA (1999) Transcripts for possible capsaicinoid biosynthetic genes are differentially accumulated in pungent and non-pungent Capsicum spp. Plant Sci 148: 47–57
20. Dal Cin V, Tieman DM, Tohge T, McQuinn R, de Vos RCH, Osorio S, Schmelz EA, Taylor MG, Smits-Kroon MT, Schuurink RC, et al (2011) Identification of genes in the phenylalanine metabolic pathway by ectopic expression of a MYB transcription factor in tomato fruit. Plant Cell 23: 2738–2753
21. Deboo GB, Albertsen MC, Taylor LP (1995) Flavanone 3-hydroxylase transcripts and flavonol accumulation are temporally coordinate in maize anthers. Plant J 7: 703–713
22. Dixon RA, Strack D (2003) Phytochemistry meets genome analysis, and beyond. Phytochemistry 62: 815–816
23. Do PT, Prudent M, Sulpice R, Causse M, Fernie AR (2010) The influence of fruit load on the tomato pericarp metabolome in a Solanum chmielewskii introgression line population. Plant Physiol 154: 1128–1142
24. Dowdle J, Ishikawa T, Gatzek S, Rolinski S, Smirnoff N (2007) Two genes in Arabidopsis thaliana encoding GDP-L-galactose phosphorylase are required for ascorbate biosynthesis and seedling viability. Plant J 52: 673–689
25. Eastmond PJ, Astley HM, Parsley K, Aubry S, Williams BP, Menard GN, Craddock CP, Nunes-Nesi A, Fernie AR, Hibberd JM (2015) Arabidopsis uses two gluconeogenic gateways for organic acids to fuel seedling establishment. Nat Commun 6: 6659
26. Edwards JS, Palsson BO (2000) The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities. Proc Natl Acad Sci USA 97: 5528–5533
27. Endler A, Meyer S, Schelbert S, Schneider T, Weschke W, Peters SW, Keller F, Baginsky S, Martinoia E, Schmidt UG (2006) Identification of a vacuolar sucrose transporter in barley and Arabidopsis mesophyll cells by a tonoplast proteomic approach. Plant Physiol 141: 196–207
28. Fernie AR (2007) The future of metabolic phytochemistry: larger numbers of metabolites, higher resolution, greater understanding. Phytochemistry 68: 2861–2880
29. Fernie AR, Klee HJ (2011) The use of natural genetic diversity in the understanding of metabolic organization and regulation. Front Plant Sci 2: 59
30. Fernie AR, Stitt M (2012) On the discordance of metabolomics with proteomics and transcriptomics: coping with increasing complexity in logic, chemistry, and network interactions. Plant Physiol 158: 1139–1145
31. Fernie AR, Trethewey RN, Krotzky AJ, Willmitzer L (2004) Metabolite profiling: from diagnostics to systems biology. Nat Rev Mol Cell Biol 5: 763–769
32. Florez-Sarasa I, Araújo WL, Wallström SV, Rasmusson AG, Fernie AR, Ribas-Carbo M (2012) Light-responsive metabolite and transcript levels are maintained following a dark-adaptation period in leaves of Arabidopsis thaliana. New Phytol 195: 136–148
33. Fukushima A, Kanaya S, Nishida K (2014) Integrated network analysis and effective tools in plant systems biology. Front Plant Sci 5: 598
34. Futuyma DJ, Agrawal AA (2009) Macroevolution and the biological diversity of plants and herbivores. Proc Natl Acad Sci USA 106: 18054–18061
35. Gatzek S, Wheeler GL, Smirnoff N (2002) Antisense suppression of L-galactose dehydrogenase in Arabidopsis thaliana provides evidence for its role in ascorbate synthesis and reveals light modulated L-galactose synthesis. Plant J 30: 541–553
36. Gechev TS, Benina M, Obata T, Tohge T, Sujeeth N, Minkov I, Hille J, Temanni MR, Marriott AS, Bergström E, et al (2013) Molecular mechanisms of desiccation tolerance in the resurrection glacial relic Haberlea rhodopensis. Cell Mol Life Sci 70: 689–709
37. Geigenberger P (2003) Response of plant metabolism to too little oxygen. Curr Opin Plant Biol 6: 247–256
38. Gholami A, De Geyter N, Pollier J, Goormachtig S, Goossens A (2014) Natural product biosynthesis in Medicago species. Nat Prod Rep 31: 356–380
39. Gibon Y, Usadel B, Blaesing OE, Kamlage B, Hoehne M, Trethewey R, Stitt M (2006) Integration of metabolite with transcript and enzyme activity profiling during diurnal cycles in Arabidopsis rosettes. Genome Biol 7: R76
40. Gigolashvili T, Yatusevich R, Rollwitz I, Humphry M, Gershenzon J, Flügge UI (2009) The plastidic bile acid transporter 5 is required for the biosynthesis of methionine-derived glucosinolates in Arabidopsis thaliana. Plant Cell 21: 1813–1829
41. Gong L, Chen W, Gao Y, Liu X, Zhang H, Xu C, Yu S, Zhang Q, Luo J (2013) Genetic analysis of the metabolome exemplified using a rice population. Proc Natl Acad Sci USA 110: 20320–20325
42. Góngora-Castillo E, Childs KL, Fedewa G, Hamilton JP, Liscombe DK, Magallanes-Lundback M, Mandadi KK, Nims E, Runguphan W, Vaillancourt B, et al (2012) Development of transcriptomic resources for interrogating the biosynthesis of monoterpene indole alkaloids in medicinal plant species. PLoS One 7: e52506
43. Guimerà R, Nunes Amaral LA (2005) Functional cartography of complex metabolic networks. Nature 433: 895–900
44. Haak DC, McGinnis LA, Levey DJ, Tewksbury JJ (2012) Why are not all chilies hot? A trade-off limits pungency. Proc Biol Sci 279: 2012–2017
45. Hannah MA, Caldana C, Steinhauser D, Balbo I, Fernie AR, Willmitzer L (2010) Combined transcript and metabolite profiling of Arabidopsis grown under widely variant growth conditions facilitates the identification of novel metabolite-mediated regulation of gene expression. Plant Physiol 152: 2120–2129
46. Hemme D, Veyel D, Mühlhaus T, Sommer F, Jüppner J, Unger AK, Sandmann M, Fehrle I, Schönfelder S, Steup M, et al (2014) Systemswide analysis of acclimation responses to long-term heat stress and recovery in the photosynthetic model organism Chlamydomonas reinhardtii. Plant Cell 26: 4270–4297
47. Hill AT, Ying S, Plaxton WC (2014) Phosphorylation of bacterial-type phosphoenolpyruvate carboxylase by a Ca2+-dependent protein kinase suggests a link between Ca2+ signalling and anaplerotic pathway control in developing castor oil seeds. Biochem J 458: 109–118
48. Hirai MY, Sugiyama K, Sawada Y, Tohge T, Obayashi T, Suzuki A, Araki R, Sakurai N, Suzuki H, Aoki K, et al (2007) Omics-based identification of Arabidopsis Myb transcription factors regulating aliphatic glucosinolate biosynthesis. Proc Natl Acad Sci USA 104: 6478–6483
49. 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
50. Hofberger JA, Lyons E, Edger PP, Pires JC, Schranz ME (2013) Whole genome and tandem duplicate retention facilitated glucosinolate pathway diversification in the mustard family. Genome Biol Evol 5: 2155–2173
51. Jander G, Norris SR, Joshi V, Fraga M, Rugg A, Yu S, Li L, Last RL (2004) Application of a high-throughput HPLC-MS/MS assay to Arabidopsis mutant screening; evidence that threonine aldolase plays a role in seed nutritional quality. Plant J 39: 465–475
52. Joseph B, Corwin JA, Kliebenstein DJ (2015) Genetic variation in the nuclear and organellar genomes modulates stochastic variation in the metabolome, growth, and defense. PLoS Genet 11: e1004779
53. Joseph B, Corwin JA, Züst T, Li B, Iravani M, Schaepman-Strub G, Turnbull LA, Kliebenstein DJ (2013) Hierarchical nuclear and cytoplasmic genetic architectures for plant growth and defense within Arabidopsis. Plant Cell 25: 1929–1945
54. Kang JH, Gonzales-Vigil E, Matsuba Y, Pichersky E, Barry CS (2014) Determination of residues responsible for substrate and product specificity of Solanum habrochaites short-chain cis-prenyltransferases. Plant Physiol 164: 80–91
55. Kim J, Kang K, Gonzales-Vigil E, Shi F, Jones AD, Barry CS, Last RL (2012) Striking natural diversity in glandular trichome acylsugar composition is shaped by variation at the Acyltransferase2 locus in the wild tomato Solanum habrochaites. Plant Physiol 160: 1854–1870
56. Kim J, Matsuba Y, Ning J, Schilmiller AL, Hammar D, Jones AD, Pichersky E, Last RL (2014) Analysis of natural and induced variation in tomato glandular trichome flavonoids identifies a gene not present in the reference genome. Plant Cell 26: 3272–3285
57. Kleessen S, Laitinen R, Fusari CM, Antonio C, Sulpice R, Fernie AR, Stitt M, Nikoloski Z (2014) Metabolic efficiency underpins performance trade-offs in growth of Arabidopsis thaliana. Nat Commun 5: 3537
58. Kliebenstein D (2009) Advancing genetic theory and application by metabolic quantitative trait loci analysis. Plant Cell 21: 1637–1646
59. Kliebenstein DJ, Lambrix VM, Reichelt M, Gershenzon J, Mitchell-Olds T (2001) Gene duplication in the diversification of secondary metabolism: tandem 2-oxoglutarate-dependent dioxygenases control glucosinolate biosynthesis in Arabidopsis. Plant Cell 13: 681–693
60. Koenig D, Jiménez-Gómez JM, Kimura S, Fulop D, Chitwood DH, Headland LR, Kumar R, Covington MF, Devisetty UK, Tat AV, et al (2013) Comparative transcriptomics reveals patterns of selection in domesticated and wild tomato. Proc Natl Acad Sci USA 110: E2655–E2662
61. Korn M, Gärtner T, Erban A, Kopka J, Selbig J, Hincha DK (2010) Predicting Arabidopsis freezing tolerance and heterosis in freezing tolerance from metabolite composition. Mol Plant 3: 224–235
62. Kusano M, Tohge T, Fukushima A, Kobayashi M, Hayashi N, Otsuki H, Kondou Y, Goto H, Kawashima M, Matsuda F, et al (2011) Metabolomics reveals comprehensive reprogramming involving two independent metabolic responses of Arabidopsis to UV-B light. Plant J 67: 354–369
63. Laing WA, Bulley S, Wright M, Cooney J, Jensen D, Barraclough D, MacRae E (2004) A highly specific L-galactose-1-phosphate phosphatase on the path to ascorbate biosynthesis. Proc Natl Acad Sci USA 101: 16976–16981
64. Laparre J, Malbreil M, Letisse F, Portais JC, Roux C, Bécard G, Puech- Pagès V (2014) Combining metabolomics and gene expression analysis reveals that propionyl- and butyryl-carnitines are involved in late stages of arbuscular mycorrhizal symbiosis. Mol Plant 7: 554–566
65. Li D, Baldwin IT, Gaquerel E (2015) Navigating natural variation in herbivory-induced secondary metabolism in coyote tobacco populations using MS/MS structural analysis. Proc Natl Acad Sci USA 112: E4147–E4155
66. Li H, Peng Z, Yang X, Wang W, Fu J, Wang J, Han Y, Chai Y, Guo T, Yang N, et al (2013) Genome-wide association study dissects the genetic architecture of oil biosynthesis in maize kernels. Nat Genet 45: 43–50
67. Lin Q, Wang C, Dong W, Jiang Q, Wang D, Li S, Chen M, Liu C, Sun C, Chen K (2015) Transcriptome and metabolome analyses of sugar and organic acid metabolism in ponkan (Citrus reticulata) fruit during fruit maturation. Gene 554: 64–74
68. Lin T, Zhu G, Zhang J, Xu X, Yu Q, Zheng Z, Zhang Z, Lun Y, Li S, Wang X, et al (2014) Genomic analyses provide insights into the history of tomato breeding. Nat Genet 46: 1220–1226
69. Luo J (2015) Metabolite-based genome-wide association studies in plants. Curr Opin Plant Biol 24: 31–38
70. Luo J, Nishiyama Y, Fuell C, Taguchi G, Elliott K, Hill L, Tanaka Y, Kitayama M, Yamazaki M, Bailey P, et al (2007) Convergent evolution in the BAHD family of acyl transferases: identification and characterization of anthocyanin acyl transferases from Arabidopsis thaliana. Plant J 50: 678–695
71. Ma F, Jazmin LJ, Young JD, Allen DK (2014) Isotopically nonstationary 13C flux analysis of changes in Arabidopsis thaliana leaf metabolism due to high light acclimation. Proc Natl Acad Sci USA 111: 16967–16972
72. Maruyama-Nakashita A, Nakamura Y, Tohge T, Saito K, Takahashi H (2006) Arabidopsis SLIM1 is a central transcriptional regulator of plant sulfur response and metabolism. Plant Cell 18: 3235–3251
73. Matas AJ, Yeats TH, Buda GJ, Zheng Y, Chatterjee S, Tohge T, Ponnala L, Adato A, Aharoni A, Stark R, et al (2011) Tissue- and cell-type specific transcriptome profiling of expanding tomato fruit provides insights into metabolic and regulatory specialization and cuticle formation. Plant Cell 23: 3893–3910
74. Matsuba Y, Nguyen TTH, Wiegert K, Falara V, Gonzales-Vigil E, Leong B, Schäfer P, Kudrna D, Wing RA, Bolger AM, et al (2013) Evolution of a complex locus for terpene biosynthesis in Solanum. Plant Cell 25: 2022–2036
75. Matsuda F, Nakabayashi R, Yang Z, Okazaki Y, Yonemaru J, Ebana K, Yano M, Saito K (2015) Metabolome-genome-wide association study dissects genetic architecture for generating natural variation in rice secondary metabolism. Plant J 81: 13–23
76. Meihls LN, Handrick V, Glauser G, Barbier H, Kaur H, Haribal MM, Lipka AE, Gershenzon J, Buckler ES, Erb M, et al (2013) Natural variation in maize aphid resistance is associated with 2,4-dihydroxy-7- methoxy-1,4-benzoxazin-3-one glucoside methyltransferase activity. Plant Cell 25: 2341–2355
77. Melanson D, Chilton MD, Masters-Moore D, Chilton WS (1997) A deletion in an indole synthase gene is responsible for the DIMBOAdeficient phenotype of bxbx maize. Proc Natl Acad Sci USA 94: 13345–13350
78. Meyer RC, Steinfath M, Lisec J, Becher M, Witucka-Wall H, Törjék O, Fiehn O, Eckardt A, Willmitzer L, Selbig J, et al (2007) The metabolic signature related to high plant growth rate in Arabidopsis thaliana. Proc Natl Acad Sci USA 104: 4759–4764
79. Mintz-Oron S, Meir S, Malitsky S, Ruppin E, Aharoni A, Shlomi T (2012) Reconstruction of Arabidopsis metabolic network models accounting for subcellular compartmentalization and tissue-specificity. Proc Natl Acad Sci USA 109: 339–344
80. Moore BD, Andrew RL, Külheim C, Foley WJ (2014) Explaining intraspecific diversity in plant secondary metabolites in an ecological context. New Phytol 201: 733–750
81. Mutwil M, Klie S, Tohge T, Giorgi FM, Wilkins O, Campbell MM, Fernie AR, Usadel B, Nikoloski Z, Persson S (2011) PlaNet: combined sequence and expression comparisons across plant networks derived from seven species. Plant Cell 23: 895–910
82. Nakabayashi R, Kusano M, Kobayashi M, Tohge T, Yonekura-Sakakibara K, Kogure N, Yamazaki M, Kitajima M, Saito K, Takayama H (2009) Metabolomics-oriented isolation and structure elucidation of 37 compounds including two anthocyanins from Arabidopsis thaliana. Phytochemistry 70: 1017–1029
83. Nakabayashi R, Saito K (2015) Integrated metabolomics for abiotic stress responses in plants. Curr Opin Plant Biol 24: 10–16
84. Nakabayashi R, Yonekura-Sakakibara K, Urano K, Suzuki M, Yamada Y, Nishizawa T, Matsuda F, Kojima M, Sakakibara H, Shinozaki K, et al (2014) Enhancement of oxidative and drought tolerance in Arabidopsis by overaccumulation of antioxidant flavonoids. Plant J 77: 367–379
85. Nakamura Y, Teo NZ, Shui G, Chua CH, Cheong WF, Parameswaran S, Koizumi R, Ohta H, Wenk MR, Ito T (2014) Transcriptomic and lipidomic profiles of glycerolipids during Arabidopsis flower development. New Phytol 203: 310–322
86. Osorio S, Alba R, Damasceno CMB, Lopez-Casado G, Lohse M, Zanor MI, Tohge T, Usadel B, Rose JKC, Fei Z, et al (2011) Systems biology of tomato fruit development: combined transcript, protein, and metabolite analysis of tomato transcription factor (nor, rin) and ethylene receptor (Nr) mutants reveals novel regulatory interactions. Plant Physiol 157: 405–425
87. Osorio S, Alba R, Nikoloski Z, Kochevenko A, Fernie AR, Giovannoni JJ (2012) Integrative comparative analyses of transcript and metabolite profiles from pepper and tomato ripening and development stages uncovers species-specific patterns of network regulatory behavior. Plant Physiol 159: 1713–1729
88. Persson S, Wei H, Milne J, Page GP, Somerville CR (2005) Identification of genes required for cellulose synthesis by regression analysis of public microarray data sets. Proc Natl Acad Sci USA 102: 8633–8638
89. Pick TR, Bräutigam A, Schlüter U, Denton AK, Colmsee C, Scholz U, Fahnenstich H, Pieruschka R, Rascher U, Sonnewald U, et al (2011) Systems analysis of a maize leaf developmental gradient redefines the current C4 model and provides candidates for regulation. Plant Cell 23: 4208–4220
90. Pollier J, Morreel K, Geelen D, Goossens A (2011) Metabolite profiling of triterpene saponins in Medicago truncatula hairy roots by liquid chromatography Fourier transform ion cyclotron resonance mass spectrometry. J Nat Prod 74: 1462–1476
91. Proost S, Van Bel M, Sterck L, Billiau K, Van Parys T, Van de Peer Y, Vandepoele K (2009) PLAZA: a comparative genomics resource to study gene and genome evolution in plants. Plant Cell 21: 3718–3731
92. Quadrana L, Almeida J, Asís R, Duffy T, Dominguez PG, Bermúdez L, Conti G, Corrêa da Silva JV, Peralta IE, Colot V, et al (2014) Natural occurring epialleles determine vitamin E accumulation in tomato fruits. Nat Commun 5: 3027
93. Riedelsheimer C, Czedik-Eysenberg A, Grieder C, Lisec J, Technow F, Sulpice R, Altmann T, Stitt M, Willmitzer L, Melchinger AE (2012) Genomic and metabolic prediction of complex heterotic traits in hybrid maize. Nat Genet 44: 217–220
94. 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. J Biol Chem 277: 43948–43960
95. Saito K, Yonekura-Sakakibara K, Nakabayashi R, Higashi Y, Yamazaki M, Tohge T, Fernie AR (2013) The flavonoid biosynthetic pathway in Arabidopsis: structural and genetic diversity. Plant Physiol Biochem 72: 21–34
96. Sauvage C, Segura V, Bauchet G, Stevens R, Do PT, Nikoloski Z, Fernie AR, Causse M (2014) Genome-wide association in tomato reveals 44 candidate loci for fruit metabolic traits. Plant Physiol 165: 1120–1132
97. Sawada Y, Toyooka K, Kuwahara A, Sakata A, Nagano M, Saito K, Hirai MY (2009) Arabidopsis bile acid:sodium symporter family protein 5 is involved in methionine-derived glucosinolate biosynthesis. Plant Cell Physiol 50: 1579–1586
98. Schauer N, Semel Y, Roessner U, Gur A, Balbo I, Carrari F, Pleban T, Perez-Melis A, Bruedigam C, Kopka J, et al (2006) Comprehensive metabolic profiling and phenotyping of interspecific introgression lines for tomato improvement. Nat Biotechnol 24: 447–454
99. Schauer N, Zamir D, Fernie AR (2005) Metabolic profiling of leaves and fruit of wild species tomato: a survey of the Solanum lycopersicum complex. J Exp Bot 56: 297–307
100. Schilmiller AL, Moghe GD, Fan P, Ghosh B, Ning J, Jones AD, Last RL (2015) Functionally divergent alleles and duplicated loci encoding an acyltransferase contribute to acylsugar metabolite diversity in Solanum trichomes. Plant Cell 27: 1002–1017
101. Schwender J, Hebbelmann I, Heinzel N, Hildebrandt T, Rogers A, Naik D, Klapperstück M, Braun HP, Schreiber F, Denolf P, et al (2015) Quantitative multilevel analysis of central metabolism in developing oilseeds of oilseed rape during in vitro culture. Plant Physiol 168: 828– 848
102. Scossa F, Brotman Y, de Abreu e Lima F, Willmitzer L, Nikoloski Z, Tohge T, Fernie AR (June 5, 2015) Genomics-based strategies for the use of natural variation in the improvement of crop metabolism. Plant Sci http://dx.doi.org/10.1016/j.plantsci.2015.05.021
103. Shelton D, Stranne M, Mikkelsen L, Pakseresht N, Welham T, Hiraka H, Tabata S, Sato S, Paquette S, Wang TL, et al (2012) Transcription factors of Lotus: regulation of isoflavonoid biosynthesis requires coordinated changes in transcription factor activity. Plant Physiol 159: 531–547
104. Simons M, Misra A, Sriram G (2014) Genome-scale models of plant metabolism. Methods Mol Biol 1083: 213–230
105. Steinfath M, Strehmel N, Peters R, Schauer N, Groth D, Hummel J, Steup M, Selbig J, Kopka J, Geigenberger P, et al (2010) Discovering plant metabolic biomarkers for phenotype prediction using an untargeted approach. Plant Biotechnol J 8: 900–911
106. Steinhauser MC, Steinhauser D, Koehl K, Carrari F, Gibon Y, Fernie AR, Stitt M (2010) Enzyme activity profiles during fruit development in tomato cultivars and Solanum pennellii. Plant Physiol 153: 80–98
107. Stephanopoulos G, Vallino JJ (1991) Network rigidity and metabolic engineering in metabolite overproduction. Science 252: 1675–1681
108. Stitt M (2013) Systems-integration of plant metabolism: means, motive and opportunity. Curr Opin Plant Biol 16: 381–388
109. Stitt M, Fernie AR (2003) From measurements of metabolites to metabolomics: an ‘on the fly’ perspective illustrated by recent studies of carbon-nitrogen interactions. Curr Opin Biotechnol 14: 136–144
110. Stitt M, Sulpice R, Keurentjes J (2010) Metabolic networks: how to identify key components in the regulation of metabolism and growth. Plant Physiol 152: 428–444
111. Sudre D, Gutierrez-Carbonell E, Lattanzio G, Rellán-Álvarez R, Gaymard F, Wohlgemuth G, Fiehn O, Alvarez-Fernández A, Zamarreño AM, Bacaicoa E, et al (2013) Iron-dependent modifications of the flower transcriptome, proteome, metabolome, and hormonal content in an Arabidopsis ferritin mutant. J Exp Bot 64: 2665–2688
112. Sulpice R, Nikoloski Z, Tschoep H, Antonio C, Kleessen S, Larhlimi A, Selbig J, Ishihara H, Gibon Y, Fernie AR, et al (2013) Impact of the carbon and nitrogen supply on relationships and connectivity between metabolism and biomass in a broad panel of Arabidopsis accessions. Plant Physiol 162: 347–363
113. Sulpice R, Pyl ET, Ishihara H, Trenkamp S, Steinfath M, Witucka-Wall H, Gibon Y, Usadel B, Poree F, Piques MC, et al (2009) Starch as a major integrator in the regulation of plant growth. Proc Natl Acad Sci USA 106: 10348–10353
114. Sulpice R, Trenkamp S, Steinfath M, Usadel B, Gibon Y, Witucka-Wall H, Pyl ET, Tschoep H, Steinhauser MC, Guenther M, et al (2010) Network analysis of enzyme activities and metabolite levels and their relationship to biomass in a large panel of Arabidopsis accessions. Plant Cell 22: 2872–2893
115. Sweetlove LJ, Fell D, Fernie AR (2008) Getting to grips with the plant metabolic network. Biochem J 409: 27–41
116. Sweetlove LJ, Fernie AR (2005) Regulation of metabolic networks: understanding metabolic complexity in the systems biology era. New Phytol 168: 9–24
117. Szecowka M, Heise R, Tohge T, Nunes-Nesi A, Vosloh D, Huege J, Feil R, Lunn J, Nikoloski Z, Stitt M, et al (2013) Metabolic fluxes in an illuminated Arabidopsis rosette. Plant Cell 25: 694–714
118. Timm S, Florian A, Wittmiß M, Jahnke K, Hagemann M, Fernie AR, Bauwe H (2013) Serine acts as a metabolic signal for the transcriptional control of photorespiration-related genes in Arabidopsis. Plant Physiol 162: 379–389
119. Töpfer N, Caldana C, Grimbs S, Willmitzer L, Fernie AR, Nikoloski Z (2013) Integration of genome-scale modeling and transcript profiling reveals metabolic pathways underlying light and temperature acclimation in Arabidopsis. Plant Cell 25: 1197–1211
120. Töpfer N, Scossa F, Fernie A, Nikoloski Z (2014) Variability of metabolite levels is linked to differential metabolic pathways in Arabidopsis’s responses to abiotic stresses. PLoS Comput Biol 10: e1003656
121. Tohge T, de Souza LP, Fernie AR (2014) Genome-enabled plant metabolomics. J Chromatogr B Analyt Technol Biomed Life Sci 966: 7–20
122. Tohge T, Fernie AR (2010) Combining genetic diversity, informatics and metabolomics to facilitate annotation of plant gene function. Nat Protoc 5: 1210–1227
123. Tohge T, Nishiyama Y, Hirai MY, Yano M, Nakajima J, Awazuhara M, Inoue E, Takahashi H, Goodenowe DB, Kitayama M, et al (2005) Functional genomics by integrated analysis of metabolome and transcriptome of Arabidopsis plants over-expressing an MYB transcription factor. Plant J 42: 218–235
124. Tohge T, Ramos MS, Nunes-Nesi A, Mutwil M, Giavalisco P, Steinhauser D, Schellenberg M, Willmitzer L, Persson S, Martinoia E, et al (2011) Toward the storage metabolome: profiling the barley vacuole. Plant Physiol 157: 1469–1482
125. Tohge T, Watanabe M, Hoefgen R, Fernie AR (2013a) The evolution of phenylpropanoid metabolism in the green lineage. Crit Rev Biochem Mol Biol 48: 123–152
126. Tohge T, Watanabe M, Hoefgen R, Fernie AR (2013b) Shikimate and phenylalanine biosynthesis in the green lineage. Front Plant Sci 4: 62
127. Tohge T, Yonekura-Sakakibara K, Niida R, Watanabe-Takahashi A, Saito K (2007) Phytochemical genomics in Arabidopsis thaliana: a case study for functional identification of flavonoid biosynthesis genes. Pure Appl Chem 79: 811–823
128. Urano K, Maruyama K, Ogata Y, Morishita Y, Takeda M, Sakurai N, Suzuki H, Saito K, Shibata D, Kobayashi M, et al (2009) Characterization of the ABA-regulated global responses to dehydration in Arabidopsis by metabolomics. Plant J 57: 1065–1078
129. Urbanczyk-Wochniak E, Luedemann A, Kopka J, Selbig J, Roessner- Tunali U, Willmitzer L, Fernie AR (2003) Parallel analysis of transcript and metabolic profiles: a new approach in systems biology. EMBO Rep 4: 989–993
130. Vallarino JG, Osorio S, Bombarely A, Casañal A, Cruz-Rus E, Sánchez- Sevilla JF, Amaya I, Giavalisco P, Fernie AR, Botella MA, et al (2015) Central role of FaGAMYB in the transition of the strawberry receptacle from development to ripening. New Phytol 208: 482–496
131. Vandepoele K, Van Bel M, Richard G, Van Landeghem S, Verhelst B, Moreau H, Van de Peer Y, Grimsley N, Piganeau G (2013) pico- PLAZA, a genome database of microbial photosynthetic eukaryotes. Environ Microbiol 15: 2147–2153
132. van der Werf MJ, Overkamp KM, Muilwijk B, Coulier L, Hankemeier T (2007) Microbial metabolomics: toward a platform with full metabolome coverage. Anal Biochem 370: 17–25
133. Vanholme R, Cesarino I, Rataj K, Xiao Y, Sundin L, Goeminne G, Kim H, Cross J, Morreel K, Araujo P, et al (2013) Caffeoyl shikimate esterase (CSE) is an enzyme in the lignin biosynthetic pathway in Arabidopsis. Science 341: 1103–1106
134. Wang L, Czedik-Eysenberg A, Mertz RA, Si Y, Tohge T, Nunes-Nesi A, Arrivault S, Dedow LK, Bryant DW, Zhou W, et al (2014) Comparative analyses of C4 and C3 photosynthesis in developing leaves of maize and rice. Nat Biotechnol 32: 1158–1165
135. Watson BS, Bedair MF, Urbanczyk-Wochniak E, Huhman DV, Yang DS, Allen SN, Li W, Tang Y, Sumner LW (2015) Integrated metabolomics and transcriptomics reveal enhanced specialized metabolism in Medicago truncatula root border cells. Plant Physiol 167: 1699–1716
136. Wen W, Li D, Li X, Gao Y, Li W, Li H, Liu J, Liu H, Chen W, Luo J, et al (2014) Metabolome-based genome-wide association study of maize kernel leads to novel biochemical insights. Nat Commun 5: 3438
137. Wheeler G, Ishikawa T, Pornsaksit V, Smirnoff N (2015) Evolution of alternative biosynthetic pathways for vitamin C following plastid acquisition in photosynthetic eukaryotes. eLife 4: 4
138. Wheeler GL, Jones MA, Smirnoff N (1998) The biosynthetic pathway of vitamin C in higher plants. Nature 393: 365–369
139. 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 Physiol 148: 704–718
140. Yonekura-Sakakibara K, Fukushima A, Nakabayashi R, Hanada K, Matsuda F, Sugawara S, Inoue E, Kuromori T, Ito T, Shinozaki K, et al (2012) Two glycosyltransferases involved in anthocyanin modification delineated by transcriptome independent component analysis in Arabidopsis thaliana. Plant J 69: 154–167
141. Yonekura-Sakakibara K, Nakabayashi R, Sugawara S, Tohge T, Ito T, Koyanagi M, Kitajima M, Takayama H, Saito K (2014) A flavonoid 3-Oglucoside: 299-O-glucosyltransferase responsible for terminal modification of pollen-specific flavonols in Arabidopsis thaliana. Plant J 79: 769–782
142. Yonekura-Sakakibara K, Saito K (2009) Functional genomics for plant natural product biosynthesis. Nat Prod Rep 26: 1466–1487
143. Yonekura-Sakakibara K, Tohge T, Matsuda F, Nakabayashi R, Takayama H, Niida R, Watanabe-Takahashi A, Inoue E, Saito K (2008) Comprehensive flavonol profiling and transcriptome coexpression analysis leading to decoding gene-metabolite correlations in Arabidopsis. Plant Cell 20: 2160–2176
144. Yonekura-Sakakibara K, Tohge T, Niida R, Saito K (2007) Identification of a flavonol 7-O-rhamnosyltransferase gene determining flavonoid pattern in Arabidopsis by transcriptome coexpression analysis and reverse genetics. J Biol Chem 282: 14932–14941
145. Young JD, Walther JL, Antoniewicz MR, Yoo H, Stephanopoulos G (2008) An elementary metabolite unit (EMU) based method of isotopically nonstationary flux analysis. Biotechnol Bioeng 99: 686–699
146. Zamboni A, Di Carli M, Guzzo F, Stocchero M, Zenoni S, Ferrarini A, Tononi P, Toffali K, Desiderio A, Lilley KS, et al (2010) Identification of putative stage-specific grapevine berry biomarkers and omics data integration into networks. Plant Physiol 154: 1439–1459
147. Zeng J, Liu Y, Liu W, Liu X, Liu F, Huang P, Zhu P, Chen J, Shi M, Guo F, et al (2013) Integration of transcriptome, proteome and metabolism data reveals the alkaloids biosynthesis in Macleaya cordata and Macleaya microcarpa. PLoS One 8: e53409
148. Zhang B, Tolstikov V, Turnbull C, Hicks LM, Fiehn O (2010) Divergent metabolome and proteome suggest functional independence of dual phloem transport systems in cucurbits. Proc Natl Acad Sci USA 107: 13532–13537