REVIEW

Functional metabolomics: from biomarker discovery to metabolome reprogramming

  • Bo Peng 2 ,
  • Hui Li 1 ,
  • Xuan-Xian Peng , 1
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  • 1. Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, MOE Key Lab Aquat Food Safety, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
  • 2. Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA

Received date: 07 May 2015

Accepted date: 28 May 2015

Published date: 11 Sep 2015

Copyright

2014 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Metabolomics is emerging as a powerful tool for studying metabolic processes, identifying crucial biomarkers responsible for metabolic characteristics and revealing metabolic mechanisms, which construct the content of discovery metabolomics. The crucial biomarkers can be used to reprogram a metabolome, leading to an aimed metabolic strategy to cope with alteration of internal and external environments, naming reprogramming metabolomics here. The striking feature on the similarity of the basic metabolic pathways and components among vastly differentspeciesmakesthe reprogrammingmetabolomics possible when the engineered metabolites play biological roles in cellular activity as a substrate of enzymes and a regulator to other molecules including proteins. The reprogramming metabolomics approach can be used to clarify metabolic mechanisms of responding to changed internal and external environmental factors and to establish a framework to develop targeted tools for dealing with the changes such as controlling and/or preventing infection with pathogens and enhancing host immunity against pathogens. This review introduces the current state and trends of discovery metabolomics and reprogramming metabolomics and highlights the importance of reprogramming metabolomics.

Cite this article

Bo Peng , Hui Li , Xuan-Xian Peng . Functional metabolomics: from biomarker discovery to metabolome reprogramming[J]. Protein & Cell, 2015 , 6(9) : 628 -637 . DOI: 10.1007/s13238-015-0185-x

1
Adamski J (2012) Genome-wide association studies with metabolomics. Genome Med 4: 34

DOI

2
Adamski J, Suhre K (2013) Metabolomics platforms for genome wide association studies—linking the genome to the metabolome. Curr Opin Biotechnol 224: 39―47

DOI

3
Bhargava P, Collins JJ (2015) Boosting bacterial metabolism to combat antibiotic resistance. Cell Metab 21: 154―155

DOI

4
Bielecka M, Watanabe M, Morcuende R, Scheible WR, Hawkesford MJ, Hesse H, Hoefgen R (2014) Transcriptome and metabolome analysis of plant sulphate starvation and resupply provides novel information on transcriptional regulation of metabolism associated with sulphur, nitrogen and phosphorus nutritional responses in Arabidopsis. Front Plant Sci 5: 805

5
Brennan L (2014) NMR-based metabolomics: from sample preparation to applications in nutrition research. Prog Nucl Magn Reson Spectrosc 83: 42―49

DOI

6
Budczies J, Pfitzner BM, Györffy B, Winzer KJ, Radke C, Dietel M, Fiehn O, Denkert C (2015) Glutamate enrichment as new diagnostic opportunity in breast cancer. Inter J Cancer 136: 1619―1628

DOI

7
Carey BW, Finley LW, Cross JR, Allis CD, Thompson CB (2015) Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature 518: 413―416

DOI

8
Castro-Santos P, Laborde CM, Diaz-Pena R (2015) Genomics, proteomics and metabolomics: their emerging roles in the discovery and validation of rheumatoid arthritis biomarkers. Clin Exp Rheumatol 33: 279―286

9
Cheng ZX, Ma YM, Li H, Peng XX (2014) N-acetylglucosamine enhances survival ability of tilapias infected by Streptococcus iniae. Fish Shellfish Immunol 40: 524―530

DOI

10
Commisso M, Strazzer P, Toffali K, Stocchero M, Guzzo F (2013) Untargeted metabolomics: an emerging approach to determine the composition of herbal products. Comput Struct Biotechnol J 4: 1―7

DOI

11
Do KT, Kastenmuller G, Mook-Kanamori DO, Yousri NA, Theis FJ, Suhre K, Krumsiek J (2015) Network-based approach for analyzing intra- and interfluid metabolite associations in human blood, urine, and saliva. J Proteome Res 14: 1183―1194

DOI

12
Dörries K, Schlueter R, Lalk M (2014) Impact of antibiotics with various target sites on the metabolome of Staphylococcus aureus. Antimicrob Agents Chemother 58: 7151―7163

DOI

13
Dudka I, Kossowska B, Senhadri H, Latajka R, Hajek J, Andrzejak R, Antonowicz-Juchniewicz J, Gancarz R (2014) Metabonomic analysis of serum of workers occupationally exposed to arsenic, cadmium and lead for biomarker research: a preliminary study. Environ Int 68: 71―81

DOI

14
Dumas ME(2012) Metabolome 2.0: quantitative genetics and network biology of metabolic phenotypes. Mol Biosyst 8: 2494―2502

DOI

15
Dumas ME, Kinross J, Nicholson JK (2014) Metabolic phenotyping and systems biology approaches to understanding metabolic syndrome and fatty liver disease. Gastroenterol 146: 46―62

DOI

16
Farag MA, Porzel A, Mahrous EA, El-Massry MM, Wessjohann LA (2015) Integrated comparative metabolite profiling via MS and NMR techniques for Senna drug quality control analysis. Anal Bioanal Chem 407: 1937―1949

DOI

17
Feng Q, Liang S, Jia H, Stadlmayr A, Tang L, Lan Z, Zhang D (2015) Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat Commun 6: 6528

DOI

18
Floegel A, Wientzek A, Bachlechner U, Jacobs S, Drogan D, Prehn C, Adamski J, Krumsiek J, Schulze M, Pischon T (2014) Linking diet, physical activity, cardiorespiratory fitness and obesity to serum metabolite networks: findings from a population-based study. Int J Obes (Lond) 38: 1388―1396

DOI

19
Fuhrer T, Zamboni N (2015) High-throughput discovery metabolomics. Curr Opin Biotechnol 31: 73―78

DOI

20
Gao P, Xu G (2015) Mass-spectrometry-based microbial metabolomics: recent developments and applications. Anal Bioanal Chem 407: 669―680

DOI

21
Ghartey J, Bastek JA, Brown AG, Anglim L, Elovitz MA (2015) Women with preterm birth have a distinct cervicovaginal metabolome. Am J Obstet Gynecol 212: 776-e1

DOI

22
Gibbons H, O’Gorman A, Brennan L (2015) Metabolomics as a tool in nutritional research. Curr Opin Lipidol 26: 30―34

DOI

23
Helms JB, Kaloyanova DV, Strating JR, van Hellemond JJ, van der Schaar HM, Tielens AG, van Kuppeveld FJ, Brouwers JF (2015) Targeting of the hydrophobic metabolome by pathogens. Traffic 16: 439―460

DOI

24
Holmes E, Wilson ID, Nicholson JK (2008) Metabolic phenotyping in health and disease. Cell 134: 714―717

DOI

25
Jorge TF, Rodrigues JA, Caldana C, Schmidt R, van Dongen JT, Thomas-Oates J, António C (2015). Mass spectrometry‐based plant metabolomics: Metabolite responses to abiotic stress. Mass Spectrom Rev.

DOI

26
Kim D, Fiske BP, Birsoy K, Freinkman E, Kami K, Possemato RL, Chudnovsky Y (2015) SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on glycine clearance. Nature 520: 363―367

DOI

27
Klähn S, Orf, Schwarz D, Matthiessen JK, Kopka J, Hess WR, Hagemann M (2015). Integrated transcriptomic and metabolomic characterization of the low-carbon response using an ndhR mutant of Synechocystis sp. PCC 6803. Plant Physiol, 144

DOI

28
Krug D, Müller R (2014) Secondary metabolomics: the impact of mass spectrometry-based approaches on the discovery and characterization of microbial natural products. Nat Prod Rep 31: 768―783

DOI

29
Kumar B, Prakash A, Ruhela RK, Medhi B (2014) Potential of metabolomics in preclinical and clinical drug development. Pharmacol Rep 66: 956―963

DOI

30
Kusuda H, Koga W, Kusano M, Oikawa A, Saito K, Hirai MY, Yoshida KT (2015) Ectopic expression of myo-inositol 3-phosphate synthase induces a wide range of metabolic changes and confers salt tolerance in rice. Plant Sci 232: 49―56

DOI

31
Li PP, Liu XJ, Li H, Peng XX (2012) Downregulation of Na (+)-NQR complex is essential for Vibrio alginolyticus in resistance to balofloxacin. J Proteomics 75: 2638―2648

DOI

32
Lin XM, Yang MJ, Li H, Wang C, Peng XX (2014) Decreased expression of LamB and Odp1 complex is crucial for antibiotic resistance in Escherichia coli. J Proteomics 98: 244―253

DOI

33
Liu X, Zhang CC, Liu Z, Wei L, Liu YJ, Yu J, Sun LX (2014) Lcbased targeted metabolomics analysis of nucleotides and identification of biomarkers associated with chemotherapeutic drugs in cultured cell models. Anti Cancer Drugs 25: 690―703

34
Ma YM, Yang MJ, Wang S, Li H, Peng XX (2015) Liver functional metabolomics discloses an action of l-leucine against Streptococcus iniae infection intilapias. Fish Shellfish Immunol 45: 414―421

DOI

35
Mahrous EA, Farag MA (2015) Two dimensional NMR spectroscopic approaches for exploring plant metabolome: A review. J Adv Res 6: 3―15

DOI

36
Mastrangelo A, Armitage EG, García A, Barbas C (2014) Metabolomics as a tool for drug discovery and personalised medicine. A review. Curr Top Med Chem 14: 2627―2636

DOI

37
Matsuda R, Bi C, Anguizola J, Sobansky M, Rodriguez E, Badilla JV, Zheng X, Hage B, Hage DS (2014) Studies of metabolite-protein interactions: a review. J Chromatogr B Analyt Technol Biomed Life Sci 966: 48―58

DOI

38
Nakabayashi R, Saito K (2015) Integrated metabolomics for abiotic stress responses in plants. Curr Opin Plant Biol 24: 10―16

DOI

39
Osanai T, Oikawa A, Iijima H, Kuwahara A, Asayama M, Tanaka K, Ikeuchi M, Saito K, Hirai MY (2014) Metabolomic analysis reveals rewiring of Synechocystis sp. PCC 6803 primary metabolism by ntcA overexpression. Environ Microbiol 16: 3304―3317

DOI

40
Patel S, Ahmed S (2015) Emerging field of metabolomics: big promise for cancer biomarker identification and drug discovery. J Pharm Biomed Anal 107: 63―74

DOI

41
Peng XX (2013) Proteomics and its applications to aquaculture in China: Infection, immunity, and interaction of aquaculture hosts with pathogens. Dev Comp Immunol 39: 63―71

DOI

42
Peng B, Su YB, Li H, Han Y, Guo C, Tian YM, Peng XX (2015a) Exogenous alanine and/or glucose plus kanamycin kills antibiotic-resistant bacteria. Cell Metab 21: 249―261

DOI

43
Peng S, Zhang J, Liu L, Zhang X, Huang Q, Alamdar A, Tian M, Shen H (2015b) Newborn meconium and urinary metabolome response to maternal gestational diabetes mellitus: a preliminary case-control study. J Proteome Res 14: 1799―1809

DOI

44
Ramautar R, Somsen GW, de Jong GJ (2015) CE-MS for metabolomics: developments and applications in the period 2012-2014. Electrophoresis 36: 212―224

DOI

45
Rojo D, Gosalbes MJ, Ferrari R, Pérez-Cobas AE, Hernández E, Oltra R, Buesa J, Latorre A, Barbas C, Ferrer M (2015). Clostridium difficile heterogeneously impacts intestinal community architecture but drives stable metabolome responses. ISME J.

DOI

46
Su YB, Peng B, Han Y, Li H, Peng XX (2015) Fructose restores susceptibility of multidrug-resistant Edwardsiella tarda to kanamycin. J Proteome Res 14: 1612―1620

DOI

47
Suhre K, Shin SY, Petersen AK, Mohney RP, Meredith D, Wägele B, Altmaier E, Deloukas P, Erdmann J, Grundberg E (2011) Human metabolic individuality in biomedical and pharmaceutical research. Nature 477: 54―60

DOI

48
Sun CX, Li MQ, Gao XX, Liu LN, Wu XF, Zhou JH (2015). Metabolic response of maize plants to multi-factorial abiotic stresses. Plant Biol (Stuttg).

DOI

49
Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, Frezza C (2013) Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 496: 238―242

DOI

50
Vázquez-Fresno R, Llorach R, Urpi-Sarda M, Lupianez-Barbero A, Estruch R, Corella D, Fitó M, Arós F, Ruiz-Canela M, Salas-Salvadó J (2014) Metabolomic pattern analysis after mediterranean diet intervention in a nondiabetic population: a 1-and 3-year follow-up in the PREDIMED study. J Proteome Res 14: 531―540

DOI

51
Wagner ND, Lankadurai BP, Simpson MJ, Simpson AJ, Frost PC (2015) Metabolomic differentiation of nutritional stress in an aquatic invertebrate. Physiol Biochem Zool 88: 43―52

DOI

52
Wang X, Mu X, Zhang J, Huang Q, Alamdar A, Tian M, Liu L, Shen H (2015) Serum metabolomics reveals that arsenic exposure disrupted lipid and amino acid metabolism in rats: a step forward in understanding chronic arsenic toxicity. Metallomics 7: 544―552

DOI

53
Weckmann K, Labermaier C, Asara J, Müller M, Turck C (2014) Time-dependent metabolomic profiling of Ketamine drug action reveals hippocampal pathway alterations and biomarker candidates. Transl Psychiatry 4: e481

DOI

54
Wolfender JL, Marti G, Thomas A, Bertrand S (2015) Current approaches and challenges for the metabolite profiling of complex natural extracts. J Chromatogr A 1382: 136―164

DOI

55
Wu CW, Zhao XL, Wu XJ, Wen C, Li H, Chen XH, Peng XX (2015) Exogenous glycine and serine promote growth and antifungal activity of Penicillium citrinum W1 from the Southwest Indian Ocean. FEMS Microbiol Lett 362: fnv040

DOI

56
Zhang J, Shen H, Xu W, Xia Y, Barr DB, Mu X, Wang X, Liu L, Huang Q, Tian M (2014) Urinary metabolomics revealed arsenic internal dose-related metabolic alterations: a proof-of-concept study in a Chinese male cohort. Environ Sci Technol 48: 12265―12274

DOI

57
Zhang Y, Zhao F, Deng Y, Zhao Y, Ren H (2015) Metagenomic and metabolomic analysis of the toxic effects of trichloroacetamideinduced gut microbiome and urine metabolome perturbations in mice. J Proteome Res 14: 1752―1761

DOI

58
Zhao XL, Wu CW, Peng XX, Li H (2014) Interferon-α2b against microbes through promoting biosynthesis of unsaturated fatty acids. J Proteome Res 13: 4155―4163

DOI

59
Zhao XL, Han Y, Ren ST, Ma YM, Li H, Peng XX (2015) l-proline increases survival of tilapias infected by Streptococcus agalactiae in higher water temperature. Fish Shellfish Immunol 44: 33―42

DOI

60
Zheng H, Kim J, Liew M, Yan JK, Herrera O, Bok JW, Kelleher NL, Keller NP, Wang Y (2015) Redox metabolites signal polymicrobial biofilm development via the NapA oxidative stress cascade in aspergillus. Curr Biol 25: 29―37

DOI

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