Metabolomics methods for the synthetic biology of secondary metabolism

FEBS Letters

Volumn 586, Issue 15, 2012, Pages 2177-2183

  Nguyen, Quoc Thai ^a   Merlo, Maria E ^a   Medema, Marnix H ^a   Jankevics, Andris ^a,b   Breitling, Rainer ^a,b   Takano, Eriko ^a  

^a UNIVERSITY OF GRONINGEN   (Netherlands)

^b UNIVERSITY OF GLASGOW   (United Kingdom)

Author keywords

Metabolomic; Secondary metabolism; Synthetic biology

Indexed keywords

NATURAL PRODUCT; UBIDECARENONE;

BACTERIAL GENE; BACTERIAL GENOME; BIOSYNTHESIS; BIOTECHNOLOGY; DNA SEQUENCE; GENE CLUSTER; GENOME ANALYSIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; LIQUID CHROMATOGRAPHY; MASS FRAGMENTOGRAPHY; METABOLISM; METABOLITE; METABOLOMICS; MICROBIOLOGY; MICROORGANISM; MOLECULAR BIOLOGY; MOLECULAR MODEL; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PREDICTION; PRIORITY JOURNAL; REVIEW; SECONDARY METABOLISM; SECONDARY METABOLITE; STRUCTURE ANALYSIS; SYNTHETIC BIOLOGY;

DRUG DISCOVERY; METABOLOMICS; MICROBIOLOGY; MODELS, BIOLOGICAL; SYNTHETIC BIOLOGY;

BACTERIA (MICROORGANISMS);

EID: 84863629449     PISSN: 00145793     EISSN: 18733468     Source Type: Journal    
DOI: 10.1016/j.febslet.2012.02.008     Document Type: Review

References (102)

1. J. Bérdy Bioactive microbial metabolites J. Antibiot. (Tokyo) 58 2005 1 26
2. M.H. Medema, M.T. Alam, R. Breitling, and E. Takano The future of industrial antibiotic production: from random mutagenesis to synthetic biology Bioeng. Bugs 2 2011 230 233
3. W. Mitchell Natural products from synthetic biology Curr. Opin. Chem. Biol. 15 2011 505 515
4. S.A. Benner, and A.M. Sismour Synthetic biology Nat. Rev. Genet. 6 2005 533 543 (Pubitemid 40910430)
5. E. Andrianantoandro, S. Basu, D.K. Karig, and R. Weiss Synthetic biology: new engineering rules for an emerging discipline Mol. Syst. Biol. 2 2006 2006 0028
6. S. Rollié, M. Mangold, and K. Sundmacher Designing biological systems: systems engineering meets synthetic biology Chem. Eng. Sci. 69 2012 1 29
7. Boyle, P.M. and Silver, P.A. (in press) Parts plus pipes: synthetic biology approaches to metabolic engineering. Metab. Eng. doi:10.1016/j.ymben. 2011.10.003.
8. R. Breitling, D. Vitkup, and M.P. Barrett New surveyor tools for charting microbial metabolic maps Nat. Rev. Microbiol. 6 2008 156 161
9. R. Goodacre, S. Vaidyanathan, W.B. Dunn, G.G. Harrigan, and D.B. Kell Metabolomics by numbers: acquiring and understanding global metabolite data Trends Biotechnol. 22 2004 245 252 (Pubitemid 38515742)
10. D.B. Kell Metabolomics and systems biology: making sense of the soup Curr. Opin. Microbiol. 7 2004 296 307 (Pubitemid 38765114)
11. K. Hollywood, D.R. Brison, and R. Goodacre Metabolomics: current technologies and future trends Proteomics 6 2006 4716 4723 (Pubitemid 44375842)
12. D.I. Ellis, and R. Goodacre Metabolomics-assisted synthetic biology Curr. Opin. Biotechnol. 23 2011 1 7
13. S.D. Bentley, K.F. Chater, A.M. Cerdeno-Tarraga, G.L. Challis, N.R. Thomson, K.D. James, D.E. Harris, M.A. Quail, H. Kieser, D. Harper, A. Bateman, S. Brown, G. Chandra, C.W. Chen, M. Collins, A. Cronin, A. Fraser, A. Goble, J. Hidalgo, T. Hornsby, S. Howarth, C.H. Huang, T. Kieser, L. Larke, L. Murphy, K. Oliver, S. O'Neil, E. Rabbinowitsch, M.A. Rajandream, K. Rutherford, S. Rutter, K. Seeger, D. Saunders, S. Sharp, R. Squares, S. Squares, K. Taylor, T. Warren, A. Wietzorrek, J. Woodward, B.G. Barrell, J. Parkhill, and D.A. Hopwood Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2) Nature 417 2002 141 147 (Pubitemid 34506788)
14. H. Ikeda, J. Ishikawa, A. Hanamoto, M. Shinose, H. Kikuchi, T. Shiba, Y. Sakaki, M. Hattori, and S. Omura Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis Nat. Biotechnol. 21 2003 526 531 (Pubitemid 36532017)
15. Y. Ohnishi, J. Ishikawa, H. Hara, H. Suzuki, M. Ikenoya, H. Ikeda, A. Yamashita, M. Hattori, and S. Horinouchi Genome sequence of the streptomycin-producing microorganism Streptomyces griseus IFO 13350 J. Bacteriol. 190 2008 4050 4060 (Pubitemid 351732884)
16. M.H. Medema, A. Trefzer, A. Kovalchuk, M. van den Berg, U. Muller, W. Heijne, L. Wu, M.T. Alam, C.M. Ronning, W.C. Nierman, R.A. Bovenberg, R. Breitling, and E. Takano The sequence of a 1.8-Mb bacterial linear plasmid reveals a rich evolutionary reservoir of secondary metabolic pathways Genome Biol. Evol. 2 2010 212 224
17. M. Fischbach, and C.A. Voigt Prokaryotic gene clusters: a rich toolbox for synthetic biology Biotechnol. J. 5 2010 1277 1296
18. M.H. Medema, R. Breitling, R. Bovenberg, and E. Takano Exploiting plug-and-play synthetic biology for drug discovery and production in microorganisms Nat. Rev. Microbiol. 9 2011 131 137
19. J. Cello, A.V. Paul, and E. Wimmer Chemical synthesis of poliovirus cDNA: generation of infectious virus in the absence of natural template Science 297 2002 1016 1018 (Pubitemid 34856035)
20. D.G. Gibson, G.A. Benders, C. Andrews-Pfannkoch, E.A. Denisova, H. Baden-Tillson, J. Zaveri, T.B. Stockwell, A. Brownley, D.W. Thomas, M.A. Algire, C. Merryman, L. Young, V.N. Noskov, J.I. Glass, J.C. Venter, C.A. Hutchison 3rd, and H.O. Smith Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome Science 319 2008 1215 1220 (Pubitemid 351323011)
21. D.K. Ro, E.M. Paradise, M. Ouellet, K.J. Fisher, K.L. Newman, J.M. Ndungu, K.A. Ho, R.A. Eachus, T.S. Ham, J. Kirby, M.C. Chang, S.T. Withers, Y. Shiba, R. Sarpong, and J.D. Keasling Production of the antimalarial drug precursor artemisinic acid in engineered yeast Nature 440 2006 940 943
22. J.D. Keasling Synthetic biology for synthetic chemistry ACS Chem. Biol. 3 2008 64 76 (Pubitemid 351227986)
23. P.K. Ajikumar, W.H. Xiao, K.E. Tyo, Y. Wang, F. Simeon, E. Leonard, O. Mucha, T.H. Phon, B. Pfeifer, and G. Stephanopoulos Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli Science 330 2010 70 74
24. M.H. Medema, R. Breitling, and E. Takano Synthetic biology in Streptomyces bacteria Methods Enzymol. 497 2011 485 502
25. M. Komatsu, T. Uchiyama, S. Omura, D.E. Cane, and H. Ikeda Genome-minimized Streptomyces host for the heterologous expression of secondary metabolism Proc. Natl. Acad. Sci. U.S.A. 107 2010 2646 2651
26. J. Nielsen, and S. Oliver The next wave in metabolome analysis Trends Biotechnol. 23 2005 544 546 (Pubitemid 41483770)
27. A. Scalbert, L. Brennan, O. Fiehn, T. Hankemeier, B.S. Kristal, B. van Ommen, E. Pujos-Guillot, E. Verheij, D. Wishart, and S. Wopereis Mass-spectrometry-based metabolomics: limitations and recommendations for future progress with particular focus on nutrition research Metabolomics 5 2009 435 458
28. Q. Hu, R.J. Noll, H. Li, A. Makarov, M. Hardman, and R. Graham Cooks The Orbitrap: a new mass spectrometer J. Mass Spectrom. 40 2005 430 443 (Pubitemid 40637866)
29. K. Dettmer, P.A. Aronov, and B.D. Hammock Mass spectrometry-based metabolomics Mass Spectrom. Rev. 26 2007 51 78 (Pubitemid 46051813)
30. M.M. Koek, R.H. Jellema, J. van der Greef, A.C. Tas, and T. Hankemeier Quantitative metabolomics based on gas chromatography mass spectrometry: status and perspectives Metabolomics 7 2011 307 328
31. D.E. Garcia, E.E. Baidoo, P.I. Benke, F. Pingitore, Y.J. Tang, S. Villa, and J.D. Keasling Separation and mass spectrometry in microbial metabolomics Curr. Opin. Microbiol. 11 2008 233 239
32. M. Merlo, A. Jankevics, E. Takano, and R. Breitling Exploring the metabolic state of microorganisms using metabolomics Bioanalysis 3 2011 2443 2458
33. R.C. De Vos, S. Moco, A. Lommen, J.J. Keurentjes, R.J. Bino, and R.D. Hall Untargeted large-scale plant metabolomics using liquid chromatography coupled to mass spectrometry Nat. Protoc. 2 2007 778 791 (Pubitemid 46745574)
34. R.D. Kersten, and P.C. Dorrestein Secondary metabolomics: natural products mass spectrometry goes global ACS Chem. Biol. 4 2009 599 601
35. M.H. Medema, K. Blin, P. Cimermancic, V. de Jager, P. Zakrzewski, M.A. Fischbach, T. Weber, E. Takano, and R. Breitling AntiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences Nucleic Acids Res. 39 2011 W339 W346
36. K. Scherlach, and C. Hertweck Triggering cryptic natural product biosynthesis in microorganisms Org. Biomol. Chem. 7 2009 1753 1760
37. G.L. Challis Mining microbial genomes for new natural products and biosynthetic pathways Microbiology 154 2008 1555 1569
38. L. Laureti, L. Song, S. Huang, C. Corre, P. Leblond, G.L. Challis, and B. Aigle Identification of a bioactive 51-membered macrolide complex by activation of a silent polyketide synthase in Streptomyces ambofaciens Proc. Natl. Acad. Sci. U.S.A. 108 2011 6258 6263
39. E. Werner, J.F. Heilier, C. Ducruix, E. Ezan, C. Junot, and J.C. Tabet Mass spectrometry for the identification of the discriminating signals from metabolomics: current status and future trends J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 871 2008 143 163
40. L. Song, F. Barona-Gomez, C. Corre, L. Xiang, D.W. Udwary, M.B. Austin, J.P. Noel, B.S. Moore, and G.L. Challis Type III polyketide synthase beta-ketoacyl-ACP starter unit and ethylmalonyl-CoA extender unit selectivity discovered by Streptomyces coelicolor genome mining J. Am. Chem. Soc. 128 2006 14754 14755 (Pubitemid 44851585)
41. A. Sandmann, J. Dickschat, H. Jenke-Kodama, B. Kunze, E. Dittmann, and R. Müller A Type II polyketide synthase from the Gram-negative bacterium Stigmatella aurantiaca is involved in aurachin alkaloid biosynthesis Angew. Chem. Int. Ed. Engl. 46 2007 2712 2716 (Pubitemid 46973570)
42. D. Krug, G. Zurek, O. Revermann, M. Vos, G.J. Velicer, and R. Müller Discovering the hidden secondary metabolome of Myxococcus xanthus: a study of intraspecific diversity Appl. Environ. Microbiol. 74 2008 3058 3068 (Pubitemid 351747010)
43. R. Bunet, L. Song, M.V. Mendes, C. Corre, L. Hotel, N. Rouhier, X. Framboisier, P. Leblond, G.L. Challis, and B. Aigle Characterization and manipulation of the pathway-specific late regulator AlpW reveals Streptomyces ambofaciens as a new producer of kinamycins J. Bacteriol. 193 2011 1142 1153
44. R. Jansen, K. Gerth, H. Steinmetz, S. Reinecke, W. Kessler, A. Kirschning, and R. Müller Elansolid A3, a unique p-quinone methide antibiotic from Chitinophaga sancti Chemistry 17 2011 7739 7744
45. W. Zander, K. Gerth, K.I. Mohr, W. Kessler, R. Jansen, and R. Müller Roimatacene: an antibiotic against Gram-negative bacteria isolated from Cystobacter ferrugineus Cb G35 (Myxobacteria) Chemistry 17 2011 7875 7881
46. W. Zander, K.I. Mohr, K. Gerth, R. Jansen, and R. Müller P-hydroxyacetophenone amides from Cystobacter ferrugineus, strain Cb G35 J. Nat. Prod. 74 2011 1358 1363
47. R.D. Kersten, Y.L. Yang, Y. Xu, P. Cimermancic, S.J. Nam, W. Fenical, M.A. Fischbach, B.S. Moore, and P.C. Dorrestein A mass spectrometry-guided genome mining approach for natural product peptidogenomics Nat. Chem. Biol. 7 2011 794 802
48. R. Carvalho, R. Reid, N. Viswanathan, H. Gramajo, and B. Julien The biosynthetic genes for disorazoles, potent cytotoxic compounds that disrupt microtubule formation Gene 359 2005 91 98 (Pubitemid 41338714)
49. R.F. Seipke, L. Song, J. Bicz, P. Laskaris, A.M. Yaxley, G.L. Challis, and R. Loria The plant pathogen Streptomyces scabies 87-22 has a functional pyochelin biosynthetic pathway that is regulated by TetR- and AfsR-family proteins Microbiology 157 2011 2681 2693
50. E. Mahenthiralingam, L. Song, A. Sass, J. White, C. Wilmot, A. Marchbank, O. Boaisha, J. Paine, D. Knight, and G.L. Challis Enacyloxins are products of an unusual hybrid modular polyketide synthase encoded by a cryptic Burkholderia ambifaria genomic island Chem. Biol. 18 2011 665 677
51. N.S. Cortina, O. Revermann, D. Krug, and R. Müller Identification and characterization of the althiomycin biosynthetic gene cluster in Myxococcus xanthus DK897 Chembiochem 12 2011 1411 1416
52. D. Pistorius, Y. Li, S. Mann, and R. Müller Unprecedented anthranilate priming involving two enzymes of the acyl adenylating superfamily in aurachin biosynthesis J. Am. Chem. Soc. 133 2011 12362 12365
53. D. Pistorius, Y. Li, A. Sandmann, and R. Müller Completing the puzzle of aurachin biosynthesis in Stigmatella aurantiaca Sg a15 Mol. Biosyst. 7 2011 3308 3315
54. L. Simmons, K. Kaufmann, R. Garcia, G. Schwar, V. Huch, and R. Müller Bendigoles D-F, bioactive sterols from the marine sponge-derived Actinomadura sp. SBMs009 Bioorg. Med. Chem. 19 2011 6570 6575
55. N.S. Cortina, D. Krug, A. Plaza, O. Revermann, and R. Müller Myxoprincomide, a novel natural product from Myxococcus xanthus discovered by a comprehensive secondary metabolome mining approach Angew. Chem. Int. Ed. 51 2012 811 816
56. J. Nielsen, and J.D. Keasling Synergies between synthetic biology and metabolic engineering Nat. Biotechnol. 29 2011 693 695
57. A.M. Weeks, and M.C. Chang Constructing de novo biosynthetic pathways for chemical synthesis inside living cells Biochemistry 50 2011 5404 5418
58. J. Nielsen It is all about metabolic fluxes J. Bacteriol. 185 2003 7031 7035 (Pubitemid 37521234)
59. D.J. Pitera, C.J. Paddon, J.D. Newman, and J.D. Keasling Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli Metab. Eng. 9 2007 193 207 (Pubitemid 46329511)
60. L. Kizer, D.J. Pitera, B.F. Pfleger, and J.D. Keasling Application of functional genomics to pathway optimization for increased isoprenoid production Appl. Environ. Microbiol. 74 2008 3229 3241 (Pubitemid 351747029)
61. S.C. Wenzel, and R. Müller The impact of genomics on the exploitation of the myxobacterial secondary metabolome Nat. Prod. Rep. 26 2009 1385 1407
62. J.D. Keasling Manufacturing molecules through metabolic engineering Science 330 2010 1355 1358
63. C.P. Cluis, A. Ekins, L. Narcross, H. Jiang, N.D. Gold, A.M. Burja, and V.J. Martin Identification of bottlenecks in Escherichia coli engineered for the production of CoQ(10) Metab. Eng. 13 2011 733 744
64. T. Hasunuma, T. Sanda, R. Yamada, K. Yoshimura, J. Ishii, and A. Kondo Metabolic pathway engineering based on metabolomics confers acetic and formic acid tolerance to a recombinant xylose-fermenting strain of Saccharomyces cerevisiae Microb. Cell Factories 10 2011 2
65. A. Jankevics, M.E. Merlo, M. de Vries, R.J. Vonk, E. Takano, and R. Breitling Metabolomic analysis of a synthetic metabolic switch in Streptomyces coelicolor A3(2) Proteomics 11 2011 4622 4631
66. K. Nieselt, F. Battke, A. Herbig, P. Bruheim, A. Wentzel, O.M. Jakobsen, H. Sletta, M.T. Alam, M.E. Merlo, J. Moore, W.A. Omara, E.R. Morrissey, M.A. Juarez-Hermosillo, A. Rodriguez-Garcia, M. Nentwich, L. Thomas, M. Iqbal, R. Legaie, W.H. Gaze, G.L. Challis, R.C. Jansen, L. Dijkhuizen, D.A. Rand, D.L. Wild, M. Bonin, J. Reuther, W. Wohlleben, M.C. Smith, N.J. Burroughs, J.F. Martin, D.A. Hodgson, E. Takano, R. Breitling, T.E. Ellingsen, and E.M. Wellington The dynamic architecture of the metabolic switch in Streptomyces coelicolor BMC Genomics 11 2010 10
67. S. Kol, M.E. Merlo, R.A. Scheltema, M. de Vries, R.J. Vonk, N.A. Kikkert, L. Dijkhuizen, R. Breitling, and E. Takano Metabolomic characterization of the salt stress response in Streptomyces coelicolor Appl. Environ. Microbiol. 76 2010 2574 2581
68. M.H. Medema, R. van Raaphorst, E. Takano, and R. Breitling Computational tools for the synthetic design of biochemical pathways Nat. Rev. Microbiol. 10 2012 191 202
69. R. Mahadevan, and C.H. Schilling The effects of alternate optimal solutions in constraint-based genome-scale metabolic models Metab. Eng. 5 2003 264 276 (Pubitemid 38122488)
70. C.S. Henry, L.J. Broadbelt, and V. Hatzimanikatis Thermodynamics-based metabolic flux analysis Biophys. J. 92 2007 1792 1805 (Pubitemid 46393490)
71. J.D. Orth, I. Thiele, and B.O. Palsson What is flux balance analysis? Nat. Biotechnol. 28 2010 245 248
72. C.S. Henry, M. DeJongh, A.A. Best, P.M. Frybarger, B. Linsay, and R.L. Stevens High-throughput generation, optimization and analysis of genome-scale metabolic models Nat. Biotechnol. 28 2010 977 982
73. M.T. Alam, M.H. Medema, E. Takano, and R. Breitling Comparative genome-scale metabolic modeling of actinomycetes: the topology of essential core metabolism FEBS Lett. 585 2011 2389 2394
74. P. May, S. Wienkoop, S. Kempa, B. Usadel, N. Christian, J. Rupprecht, J. Weiss, L. Recuenco-Munoz, O. Ebenhoh, W. Weckwerth, and D. Walther Metabolomics- and proteomics-assisted genome annotation and analysis of the draft metabolic network of Chlamydomonas reinhardtii Genetics 179 2008 157 166
75. M.T. Alam, M.E. Merlo, STREAM Consortium, D.A. Hodgson, E.M. Wellington, E. Takano, and R. Breitling Metabolic modeling and analysis of the metabolic switch in Streptomyces coelicolor BMC Genomics 11 2010 202
76. M.H. Medema, M.T. Alam, W.H. Heijne, M.A. van den Berg, U. Muller, A. Trefzer, R.A. Bovenberg, R. Breitling, and E. Takano Genome-wide gene expression changes in an industrial clavulanic acid overproduction strain of Streptomyces clavuligerus Microb. Biotechnol. 4 2011 300 305
77. 13C isotopic labeling Mass Spectrom. Rev. 28 2009 362 375
78. 13C-flux analysis Curr. Opin. Microbiol. 12 2009 553 558
79. M. Dauner From fluxes and isotope labeling patterns towards in silico cells Curr. Opin. Biotechnol. 21 2010 55 62
80. C.L. Winder, W.B. Dunn, and R. Goodacre TARDIS-based microbial metabolomics: time and relative differences in systems Trends Microbiol. 19 2011 315 322
81. K. Nöh, and W. Wiechert The benefits of being transient: isotope-based metabolic flux analysis at the short time scale Appl. Microbiol. Biotechnol. 91 2011 1247 1265
82. K. Schneider, R. Peyraud, P. Kiefer, P. Christen, N. Delmotte, S. Massou, J.C. Portais, and J.A. Vorholt The ethylmalonyl-CoA pathway is used in place of the glyoxylate cycle by Methylobacterium extorquens AM1 during growth on acetate J. Biol. Chem. 287 2012 757 766
83. R. Peyraud, K. Schneider, P. Kiefer, S. Massou, J.A. Vorholt, and J.C. Portais Genome-scale reconstruction and system level investigation of the metabolic network of Methylobacterium extorquens AM1 BMC Syst. Biol. 5 2011 189
84. 13C metabolomics Proc. Natl. Acad. Sci. U.S.A. 106 2009 4846 4851
85. Salimi, F., Mandal, R., Wishart, D. and Mahadevan, R. (2010) Understanding Clostridium acetobutylicum ATCC 824 metabolism using genome-scale thermodynamics and metabolomics-based modeling. In: Proceedings of the 11th International Symposium on Computer Applications in Biotechnology (CAB 2010), Leuven, Belgium, July 7-9, 2010.
86. T. Kind, and O. Fiehn What are the obstacles for an integrated system for comprehensive interpretation of cross-platform metabolic profile data? Bioanalysis 1 2009 1511 1514
87. M.J. van der Werf, K.M. Overkamp, B. Muilwijk, L. Coulier, and T. Hankemeier Microbial metabolomics: toward a platform with full metabolome coverage Anal. Biochem. 370 2007 17 25 (Pubitemid 47404495)
88. M. Liebeke, K. Dorries, D. Zuhlke, J. Bernhardt, S. Fuchs, J. Pane-Farre, S. Engelmann, U. Volker, R. Bode, T. Dandekar, U. Lindequist, M. Hecker, and M. Lalk A metabolomics and proteomics study of the adaptation of Staphylococcus aureus to glucose starvation Mol. Biosyst. 7 2011 1241 1253
89. T. Kind, and O. Fiehn Advances in structure elucidation of small molecules using mass spectrometry Bioanal. Rev. 2 2010 23 60
90. D.J. Creek, A. Jankevics, R. Breitling, D.G. Watson, M.P. Barrett, and K.E. Burgess Toward global metabolomics analysis with hydrophilic interaction liquid chromatography-mass spectrometry: improved metabolite identification by retention time prediction Anal. Chem. 83 2011 8703 8710
91. G.J. Patti Separation strategies for untargeted metabolomics J. Sep. Sci. 34 2011 3460 3469
92. S. Wolf, S. Schmidt, M. Muller-Hannemann, and S. Neumann In silico fragmentation for computer assisted identification of metabolite mass spectra BMC Bioinformatics 11 2010 148
93. H. Horai, M. Arita, S. Kanaya, Y. Nihei, T. Ikeda, K. Suwa, Y. Ojima, K. Tanaka, S. Tanaka, K. Aoshima, Y. Oda, Y. Kakazu, M. Kusano, T. Tohge, F. Matsuda, Y. Sawada, M.Y. Hirai, H. Nakanishi, K. Ikeda, N. Akimoto, T. Maoka, H. Takahashi, T. Ara, N. Sakurai, H. Suzuki, D. Shibata, S. Neumann, T. Iida, K. Tanaka, K. Funatsu, F. Matsuura, T. Soga, R. Taguchi, K. Saito, and T. Nishioka MassBank: a public repository for sharing mass spectral data for life sciences J. Mass Spectrom. 45 2010 703 714
94. C.A. Smith, G. O'Maille, E.J. Want, C. Qin, S.A. Trauger, T.R. Brandon, D.E. Custodio, R. Abagyan, and G. Siuzdak METLIN: a metabolite mass spectral database Ther. Drug Monit. 27 2005 747 751 (Pubitemid 44391729)
95. D.S. Wishart, C. Knox, A.C. Guo, R. Eisner, N. Young, B. Gautam, D.D. Hau, N. Psychogios, E. Dong, S. Bouatra, R. Mandal, I. Sinelnikov, J. Xia, L. Jia, J.A. Cruz, E. Lim, C.A. Sobsey, S. Shrivastava, P. Huang, P. Liu, L. Fang, J. Peng, R. Fradette, D. Cheng, D. Tzur, M. Clements, A. Lewis, A. De Souza, A. Zuniga, M. Dawe, Y. Xiong, D. Clive, R. Greiner, A. Nazyrova, R. Shaykhutdinov, L. Li, H.J. Vogel, and I. Forsythe HMDB: a knowledgebase for the human metabolome Nucleic Acids Res. 37 2009 D603 D610
96. E.E. Bolton, Y. Wang, P.A. Thiessen, and S.H. Bryant Chapter 12 PubChem: integrated platform of small molecules and biological activities Annu. Rep. Comput. Chem. 4 2008 217 241
97. T.F. Molinski NMR of natural products at the "nanomole-scale" Nat. Prod. Rep. 27 2010 321 329
98. R. Kwok Five hard truths for synthetic biology Nature 463 2010 288 290
99. N. Szita, K. Polizzi, N. Jaccard, and F. Baganz Microfluidic approaches for systems and synthetic biology Curr. Opin. Biotechnol. 21 2010 517 523
100. P. Vinuselvi, S. Park, M. Kim, J.M. Park, T. Kim, and S.K. Lee Microfluidic technologies for synthetic biology Int. J. Mol. Sci. 12 2011 3576 3593
101. J.R. Kraly, R.E. Holcomb, Q. Guan, and C.S. Henry Review: microfluidic applications in metabolomics and metabolic profiling Anal. Chim. Acta 653 2009 23 35
102. M. Heinemann, and R. Zenobi Single cell metabolomics Curr. Opin. Biotechnol. 22 2011 26 31