Metabolomics: A Microbial Physiology and Metabolism Perspective

  • Chijioke J. Joshua
Part of the Methods in Molecular Biology book series (MIMB, volume 1859)


Metabolomics is valuable for studying microbial metabolism, which is often used to elucidate biological functions. Effective application of metabolomics is enhanced by fundamental understanding of microbial physiology and metabolism. This review briefly highlights important aspects of metabolism that are essential for designing and executing effective metabolic and metabolomics studies. The influence of microbial physiology and metabolism on growth, energy metabolism and regulation is briefly reviewed. The chapter also evaluates factors affecting metabolic prediction.

Key words

Microbial physiology Microbial metabolism Microbial growth Central carbon metabolism Metabolic regulation Experimental design Metabolic pathways 



This work was part of the DOE Joint BioEnergy Institute ( supported by the US Department of Energy, Office of Science, Office of Biological and Environmental Research, through contract DE-AC02-05CH11231 between Lawrence Berkeley National Laboratory and the US Department of Energy.


  1. 1.
    Crick F (1970) Central dogma of molecular biology. Nature 227:561–563CrossRefGoogle Scholar
  2. 2.
    Schreiber SL (2005) Small molecules: the missing link in the central dogma. Nat Chem Biol 1:64–66CrossRefGoogle Scholar
  3. 3.
    Metallo CM, Vander Heiden MG (2013) Understanding metabolic regulation and its influence on cell physiology. Mol Cell 49:388–398CrossRefGoogle Scholar
  4. 4.
    Marson A, Levine SS, Cole MF, Frampton GM, Brambrink T, Johnstone S, Guenther MG, Johnston WK, Wernig M, Newman J, Calabrese JM, Dennis LM, Volkert TL, Gupta S, Love J, Hannett N, Sharp PA, Bartel DP, Jaenisch R, Young RA (2008) Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell 134:521–533CrossRefGoogle Scholar
  5. 5.
    Reik W (2007) Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447:425–432CrossRefGoogle Scholar
  6. 6.
    Rochfort S (2005) Metabolomics reviewed: a new “omics” platform technology for systems biology and implications for natural products research. J Nat Prod 68:1813–1820CrossRefGoogle Scholar
  7. 7.
    McLean TI (2013) “Eco-omics”: a review of the application of genomics, transcriptomics, and proteomics for the study of the ecology of harmful algae. Microb Ecol 65:901–915CrossRefGoogle Scholar
  8. 8.
    Monod J (1949) The growth of bacterial cultures. Annu Rev Microbiol 3:371–394CrossRefGoogle Scholar
  9. 9.
    Larsson U, Hörstedt P, Normark S (1979) Frequency of dividing cells, a new approach to the determination of bacterial growth rates in aquatic environments. Appl Environ Microbiol 37:805–812PubMedPubMedCentralGoogle Scholar
  10. 10.
    Maier RM, Pepper I, Gerba C (2000) Bacterial growth. Environ Microbiol 2000:43–59Google Scholar
  11. 11.
    Peleg M, Corradini MG (2011) Microbial growth curves: what the models tell us and what they cannot. Crit Rev Food Sci Nutr 51:917–945CrossRefGoogle Scholar
  12. 12.
    Herbert D, Elsworth R, Telling R (1956) The continuous culture of bacteria; a theoretical and experimental study. Microbiology 14:601–622Google Scholar
  13. 13.
    Joshua CJ, Dahl R, Benke PI, Keasling JD (2011) Absence of diauxie during simultaneous utilization of glucose and xylose by Sulfolobus acidocaldarius. J Bacteriol 193:1293–1301CrossRefGoogle Scholar
  14. 14.
    Baranyi J, Roberts TA (1994) A dynamic approach to predicting bacterial growth in food. Int J Food Microbiol 23:277–294CrossRefGoogle Scholar
  15. 15.
    Rolfe MD, Rice CJ, Lucchini S, Pin C, Thompson A, Cameron ADS, Alston M, Stringer MF, Betts RP, Baranyi J, Peck MW, Hinton JCD (2012) Lag phase is a distinct growth phase that prepares bacteria for exponential growth and involves transient metal accumulation. J Bacteriol 194:686–701CrossRefGoogle Scholar
  16. 16.
    Joshua CJ, Perez LD, Keasling JD (2013) Functional characterization of the origin of replication of pRN1 from Sulfolobus islandicus REN1H1. PLoS One 8:e84664CrossRefGoogle Scholar
  17. 17.
    Saldanha AJ, Brauer MJ, Botstein D (2004) Nutritional homeostasis in batch and steady-state culture of yeast. Mol Biol Cell 15:4089–4104CrossRefGoogle Scholar
  18. 18.
    Monod J (1942) Recherches sur la croissance des cultures bactâeriennes. Hermann, ParisGoogle Scholar
  19. 19.
    Kolter R, Siegele DA, Tormo A (1993) The stationary phase of the bacterial life cycle. Annu Rev Microbiol 47:855–874CrossRefGoogle Scholar
  20. 20.
    Brown JV, Wiles R, Prentice GA (1979) The effect of a modified tyndallization process upon the sporeforming bacteria of milk and cream. Int J Dairy Technol 32:109–112CrossRefGoogle Scholar
  21. 21.
    Finkel SE (2006) Long-term survival during stationary phase: evolution and the GASP phenotype. Nat Rev Microbiol 4:113–120CrossRefGoogle Scholar
  22. 22.
    Gorke B, Stulke J (2008) Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Nat Rev Microbiol 6:613–624CrossRefGoogle Scholar
  23. 23.
    Magasanik B (1961) Catabolite repression. Cold Spring Harb Symp Quant Biol 26:249–256CrossRefGoogle Scholar
  24. 24.
    Sudarsan S, Dethlefsen S, Blank LM, Siemann-Herzberg M, Schmid A (2014) The functional structure of central carbon metabolism in Pseudomonas putida KT2440. Appl Environ Microbiol 80:5292–5303CrossRefGoogle Scholar
  25. 25.
    Sulpice R, McKeown PC (2015) Moving toward a comprehensive map of central plant metabolism. Annu Rev Plant Biol 66:187–210CrossRefGoogle Scholar
  26. 26.
    Brouqui P, Raoult D (2001) Endocarditis due to rare and fastidious bacteria. Clin Microbiol Rev 14:177–207CrossRefGoogle Scholar
  27. 27.
    Gray CT, Wimpenny JWT, Hughes D, Mossman MR (1966) Regulation of metabolism in facultative bacteria: 1. Structural and functional changes in Escherichia coli associated with shifts between the aerobic and anaerobic states. Biochim Biophys Acta 117:22–32CrossRefGoogle Scholar
  28. 28.
    Chen X, Schreiber K, Appel J, Makowka A, Fähnrich B, Roettger M, Hajirezaei MR, Sönnichsen FD, Schönheit P, Martin WF (2016) The Entner–Doudoroff pathway is an overlooked glycolytic route in cyanobacteria and plants. Proc Natl Acad Sci 113:5441–5446CrossRefGoogle Scholar
  29. 29.
    Kengen SW, de Bok FA, van Loo ND, Dijkema C, Stams AJ, de Vos WM (1994) Evidence for the operation of a novel Embden-Meyerhof pathway that involves ADP-dependent kinases during sugar fermentation by Pyrococcus furiosus. J Biol Chem 269:17537–17541PubMedGoogle Scholar
  30. 30.
    Gautheron DC (1984) Mitochondrial oxidative phosphorylation and respiratory chain: review. J Inherit Metab Dis 7:57–61CrossRefGoogle Scholar
  31. 31.
    Chaban Y, Boekema EJ, Dudkina NV (2014) Structures of mitochondrial oxidative phosphorylation supercomplexes and mechanisms for their stabilisation. Biochim Biophys Acta 1837:418–426CrossRefGoogle Scholar
  32. 32.
    Fernie AR, Carrari F, Sweetlove LJ (2004) Respiratory metabolism: glycolysis, the TCA cycle and mitochondrial electron transport. Curr Opin Plant Biol 7:254–261CrossRefGoogle Scholar
  33. 33.
    Gel’man NS, Lukoyanova MA, Ostrovskii DN (1967) Oxidative phosphorylation in bacteria. In: Gel’man NS, Lukoyanova MA, Ostrovskii DN (eds) Respiration and phosphorylation of bacteria. Springer, Boston, MA, pp 161–192. Scholar
  34. 34.
    Saraste M (1999) Oxidative Phosphorylation at the fin de siècle. Science 283:1488CrossRefGoogle Scholar
  35. 35.
    Wamelink MMC, Struys EA, Jakobs C (2008) The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review. J Inherit Metab Dis 31:703–717CrossRefGoogle Scholar
  36. 36.
    Clark DP (1989) The fermentation pathways of Escherichia coli. FEMS Microbiol Rev 5:223–234PubMedGoogle Scholar
  37. 37.
    Spaans SK, Weusthuis RA, van der Oost J, Kengen SWM (2015) NADPH-generating systems in bacteria and archaea. Front Microbiol 6:742CrossRefGoogle Scholar
  38. 38.
    Fuhrer T, Sauer U (2009) Different biochemical mechanisms ensure network-wide balancing of reducing equivalents in microbial metabolism. J Bacteriol 191:2112–2121CrossRefGoogle Scholar
  39. 39.
    Horecker BL (2002) The pentose phosphate pathway. J Biol Chem 277:47965–47971CrossRefGoogle Scholar
  40. 40.
    Lenzen S (2014) A fresh view of glycolysis and glucokinase regulation: history and current status. J Biol Chem 289:12189–12194CrossRefGoogle Scholar
  41. 41.
    Martin SA, Russell JB (1986) Phosphoenolpyruvate-dependent phosphorylation of hexoses by ruminal bacteria: evidence for the phosphotransferase transport system. Appl Environ Microbiol 52:1348–1352PubMedPubMedCentralGoogle Scholar
  42. 42.
    Verhees CH, Kengen SWM, Tuininga JE, Schut GJ, Adams MWW, De Vos WM, Van der Oost J (2004) The unique features of glycolytic pathways in Archaea. Biochem J 377:819–822CrossRefGoogle Scholar
  43. 43.
    Ahmed H, Ettema TJG, Tjaden B, Geerling ACM, van der Oost J, Siebers B (2005) The semi-phosphorylative EntnerDoudoroff pathway in hyperthermophilic archaea: a re-evaluation. Biochem J 390:529–540CrossRefGoogle Scholar
  44. 44.
    Snijders APL, Walther J, Peter S, Kinnman I, de Vos MG, van de Werken HJ, SJJ B, van der Oost J, Wright PC (2006) Reconstruction of central carbon metabolism in Sulfolobus solfataricus using a two-dimensional gel electrophoresis map, stable isotope labelling and DNA microarray analysis. Proteomics 6:1518–1529CrossRefGoogle Scholar
  45. 45.
    Kengen SWM (2017) Pyrococcus furiosus, 30 years on. J Microbial Biotechnol 10:1441–1444CrossRefGoogle Scholar
  46. 46.
    Kengen SM, Stams AJM, de Vos WM (1996) Sugar metabolism of hyperthermophiles. FEMS Microbiol Rev 18:119–137CrossRefGoogle Scholar
  47. 47.
    Imanaka H, Yamatsu A, Fukui T, Atomi H, Imanaka T (2006) Phosphoenolpyruvate synthase plays an essential role for glycolysis in the modified Embden-Meyerhof pathway in Thermococcus kodakarensis. Mol Microbiol 61:898–909CrossRefGoogle Scholar
  48. 48.
    Sakuraba H, Utsumi EMI, Schreier HJ, Ohshima T (2001) Transcriptional regulation of phosphoenolpyruvate synthase by maltose in the hyperthermophilic Archaeon, Pyrococcus furiosus. Soc Biotechnol 92:108–113Google Scholar
  49. 49.
    Akram M (2014) Citric acid cycle and role of its intermediates in metabolism. Cell Biochem Biophys 68:475–478CrossRefGoogle Scholar
  50. 50.
    Sugden MC, Holness MJ (2003) Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs. Am J Physiol Endocrinol Metab 284:E855CrossRefGoogle Scholar
  51. 51.
    Berg IA (2011) Ecological aspects of the distribution of different autotrophic CO2 fixation pathways. Appl Environ Microbiol 77:1925–1936CrossRefGoogle Scholar
  52. 52.
    Hügler M, Wirsen CO, Fuchs G, Taylor CD, Sievert SM (2005) Evidence for autotrophic CO2 fixation via the reductive tricarboxylic acid cycle by members of the ε subdivision of Proteobacteria. J Bacteriol 187:3020–3027CrossRefGoogle Scholar
  53. 53.
    Tang K-H, Blankenship RE (2010) Both forward and reverse TCA cycles operate in green sulfur bacteria. J Biol Chem 285:35848–35854CrossRefGoogle Scholar
  54. 54.
    Buchanan BB, Arnon DI (1990) A reverse KREBS cycle in photosynthesis: consensus at last. Photosynth Res 24:47–53CrossRefGoogle Scholar
  55. 55.
    Hers HG, Hue L (1983) Gluconeogenesis and related aspects of glycolysis. Annu Rev Biochem 52:617–653CrossRefGoogle Scholar
  56. 56.
    Pilkis SJ, Granner DK (1992) Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis. Annu Rev Physiol 54:885–909CrossRefGoogle Scholar
  57. 57.
    Chulavatnatol M, Atkinson DE (1973) Phosphoenolpyruvate synthetase from Escherichia coli: effects of adenylate energy charge and modifier concentrations. J Biol Chem 248:2712–2715PubMedGoogle Scholar
  58. 58.
    Owen OE, Kalhan SC, Hanson RW (2002) The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem 277:30409–30412CrossRefGoogle Scholar
  59. 59.
    Jablonsky J, Papacek S, Hagemann M (2016) Different strategies of metabolic regulation in cyanobacteria: from transcriptional to biochemical control. Sci Rep 6:33024CrossRefGoogle Scholar
  60. 60.
    Shimizu K (2013) Metabolic regulation of a bacterial cell system with emphasis on Escherichia coli metabolism. ISRN Biochem 2013:47CrossRefGoogle Scholar
  61. 61.
    Chubukov V, Gerosa L, Kochanowski K, Sauer U (2014) Coordination of microbial metabolism. Nat Rev Microbiol 12:327–340CrossRefGoogle Scholar
  62. 62.
    Gray LR, Tompkins SC, Taylor EB (2014) Regulation of pyruvate metabolism and human disease. Cell Mol Life Sci 71:2577–2604CrossRefGoogle Scholar
  63. 63.
    Erkut C, Gade VR, Laxman S, Kurzchalia TV (2016) The glyoxylate shunt is essential for desiccation tolerance in C elegans and budding yeast. Elife 5:e13614CrossRefGoogle Scholar
  64. 64.
    Cerdán S, Rodrigues TB, Sierra A, Benito M, Fonseca LL, Fonseca CP, García-Martín ML (2006) The redox switch/redox coupling hypothesis. Neurochem Int 48:523–530CrossRefGoogle Scholar
  65. 65.
    Draoui N, Feron O (2011) Lactate shuttles at a glance: from physiological paradigms to anti-cancer treatments. Dis Model Mech 4:727–732CrossRefGoogle Scholar
  66. 66.
    Larsson C, Påhlman IL, Ansell R, Rigoulet M, Adler L, Gustafsson L (1998) The importance of the glycerol 3-phosphate shuttle during aerobic growth of Saccharomyces cerevisiae. Yeast (Chichester, Engl) 14:347–357CrossRefGoogle Scholar
  67. 67.
    Henningsen BM, Hon S, Covalla SF, Sonu C, Argyros DA, Barrett TF, Wiswall E, Froehlich AC, Zelle RM (2015) Increasing anaerobic acetate consumption and ethanol yields in Saccharomyces cerevisiae with NADPH-specific alcohol dehydrogenase. Appl Environ Microbiol 81:8108–8117CrossRefGoogle Scholar
  68. 68.
    Hagopian K, Ramsey JJ, Weindruch R (2008) Enzymes of glycerol and glyceraldehyde metabolism in mouse liver: effects of caloric restriction and age on activities. Biosci Rep 28:107–115PubMedPubMedCentralGoogle Scholar
  69. 69.
    Cheeseman AJ, Clark JB (1988) Influence of the malate-aspartate shuttle on oxidative metabolism in synaptosomes. J Neurochem 50:1559–1565CrossRefGoogle Scholar
  70. 70.
    Ahn S, Jung J, Jang I-A, Madsen EL, Park W (2016) Role of glyoxylate shunt in oxidative stress response. J Biol Chem 291:11928–11938CrossRefGoogle Scholar
  71. 71.
    Dunn MF, Ramírez-Trujillo JA, Hernández-Lucas I (2009) Major roles of isocitrate lyase and malate synthase in bacterial and fungal pathogenesis. Microbiology 155:3166–3175CrossRefGoogle Scholar
  72. 72.
    Wolfe AJ (2005) The acetate switch. Microbiol Mol Biol Rev 69:12–50CrossRefGoogle Scholar
  73. 73.
    Maloy SR, Bohlander M, Nunn WD (1980) Elevated levels of glyoxylate shunt enzymes in Escherichia coli strains constitutive for fatty acid degradation. J Bacteriol 143:720–725PubMedPubMedCentralGoogle Scholar
  74. 74.
    Alonso-Gutierrez J, Chan R, Batth TS, Adams PD, Keasling JD, Petzold CJ, Lee TS (2013) Metabolic engineering of Escherichia coli for limonene and perillyl alcohol production. Metab Eng 19:33–41CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Chijioke J. Joshua
    • 1
    • 2
  1. 1.Biological Systems and Engineering DivisionLawrence Berkeley National LaboratoryBerkeleyUSA
  2. 2.Joint BioEnergy InstituteEmeryvilleUSA

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