Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

In situ to in silico and back: elucidating the physiology and ecology of Geobacter spp. using genome-scale modelling

An Erratum to this article was published on 16 February 2011

This article has been updated

Key Points

  • Advances in sequencing technologies have enabled the detailed characterization of microbial genomes and environmental metagenomes.

  • These genomes have been the basis for the reconstruction of detailed metabolic networks and models for several microorganisms.

  • Geobacter spp., with their unique ability for extracellular electron transfer, are examples of such organisms and have important applications in bioremediation and microbial fuel cells.

  • In addition to helping to derive an in-depth understanding of the physiology and metabolism of Geobacter spp., genome-scale modelling was valuable in helping to describe microbial ecology and, in particular, the competition of these species with other Fe III reducers.

  • Integration of the recently developed automated pipeline for metabolic modelling with physiology experiments will allow researchers to use the modelling approaches described here for the characterization of other environmentally relevant microorganisms.

Abstract

There is a wide diversity of unexplored metabolism encoded in the genomes of microorganisms that have an important environmental role. Genome-scale metabolic modelling enables the individual reactions that are encoded in annotated genomes to be organized into a coherent whole, which can then be used to predict metabolic fluxes that will optimize cell function under a range of conditions. In this Review, we summarize a series of studies in which genome-scale metabolic modelling of Geobacter spp. has resulted in an in-depth understanding of their central metabolism and ecology. A similar iterative modelling and experimental approach could accelerate elucidation of the physiology and ecology of other microorganisms inhabiting a diversity of environments, and could guide optimization of the practical applications of these species.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Iterative and integrated experimental and computational methodology for studying the physiology and metabolism of Geobacter spp.
Figure 2: Model-based insights into acetate and isoleucine metabolism in Geobacter spp.
Figure 3: Alternative mechanisms for maintaining metabolic robustness in microorganisms with different metabolic capabilities.
Figure 4: Proton accumulation during substrate oxidation.
Figure 5: Model-aided metabolic engineering of Geobacter sulfurreducens through the introduction of a futile cycle that leads to increased respiration as well as reduced biomass synthesis.
Figure 6: Genome-scale constraint-based models for the prediction of microbial composition as a function of the environment.
Figure 7: Coupling metabolic models with transport and geochemical models.

Change history

  • 05 January 2011

    In the original article, the Acknowledgements section was omitted; this section has now been included: Acknowledgements: We acknowledge the US Department of Energy's Genomic Science Program (cooperative agreement DE-FC02-02ER63446) and Subsurface Biogeochemical Research Program (grant DE-FG02-07ER64367) for funding, and C. O'Connell for help with the illustrations. We apologize for this omission.

References

  1. Feist, A. M., Herrgard, M. J., Thiele, I., Reed, J. L. & Palsson, B. O. Reconstruction of biochemical networks in microorganisms. Nature Rev. Microbiol. 7, 129–143 (2009).

    Article  CAS  Google Scholar 

  2. Oberhardt, M. A., Palsson, B. O. & Papin, J. A. Applications of genome-scale metabolic reconstructions. Mol. Syst. Biol. 5, 320 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Thiele, I. & Palsson, B. O. A protocol for generating a high-quality genome-scale metabolic reconstruction. Nature Protoc. 5, 93–121 (2010). This paper provides a comprehensive 96-step protocol for reconstructing a metabolic network based on genome sequence and physiology, followed by evaluation of the network through the use of constraint-based modelling.

    Article  CAS  Google Scholar 

  4. Reed, J. L., Famili, I., Thiele, I. & Palsson, B. O. Towards multidimensional genome annotation. Nature Rev. Genet. 7, 130–141 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Palsson, B. in Systems Biology: Properties of Reconstructed Networks (Cambridge Univ. Press, New York, 2006).

    Book  Google Scholar 

  6. Feist, A. M. et al. A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information. Mol. Syst. Biol. 3, 121 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Joyce, A. R. & Palsson, B. O. Toward whole cell modeling and simulation: comprehensive functional genomics through the constraint-based approach. Prog. Drug Res. 64, 265–309 (2007).

    Article  CAS  PubMed  Google Scholar 

  8. Orth, J. D., Thiele, I. & Palsson, B. O. What is flux balance analysis? Nature Biotech. 28, 245–248 (2010).

    Article  CAS  Google Scholar 

  9. Mo, M. L. & Palsson, B. O. Understanding human metabolic physiology: a genome-to-systems approach Trends Biotechnol. 27, 37–44 (2009).

    Article  CAS  PubMed  Google Scholar 

  10. Duarte, N. D. et al. Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proc. Natl Acad. Sci. 104, 1777–1782 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Feist, A. M. & Palsson, B. O. The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli. Nature Biotech. 26, 659–667 (2008).

    Article  CAS  Google Scholar 

  12. Herrgard, M. J. et al. A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology. Nature Biotech. 26, 1155–1160 (2008).

    Article  CAS  Google Scholar 

  13. Oh, Y. K., Palsson, B. O., Park, S. M., Schilling, C. H. & Mahadevan, R. Genome-scale reconstruction of metabolic network in Bacillus subtilis based on high-throughput phenotyping and gene essentiality data. J. Biol. Chem. 282, 28791–28799 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Connon, S. A. & Giovannoni, S. J. High-throughput methods for culturing microorganisms in very-low-nutrient media yield diverse new marine isolates. Appl. Environ. Microbiol. 68, 3878–3885 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kaeberlein, T., Lewis, K. & Epstein, S. S. Isolating “uncultivable” microorganisms in pure culture in a simulated natural environment. Science 296, 1127–1129 (2002).

    Article  CAS  PubMed  Google Scholar 

  16. Lovley, D. R., Holmes, D. E. & Nevin, K. P. Dissimilatory Fe(III) and Mn(IV) reduction. Adv. Microb. Physiol. 49, 219–286 (2004). A detailed introduction to the physiology and ecology of Geobacter spp. as well as other metal reducers.

    Article  CAS  PubMed  Google Scholar 

  17. Lovley, D. R., Stolz, J. F., Nord., G. L. & Phillips, E. J. P. Anaerobic production of magnetite by a dissimilatory iron-reducing microorganism. Nature 330, 252–254 (1987).

    Article  CAS  Google Scholar 

  18. Lovley, D. R. & Phillips, E. J. P. Novel mode of microbial energy-metabolism - organic-carbon oxidation coupled to dissimilatory reduction of iron or manganese. Appl. Environ. Microbiol. 54, 1472–1480 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Lovley, D. R. et al. Geobacter metallireducens gen. nov. sp. nov., a microorganism capable of coupling the complete oxidation of organic compounds to the reduction of iron and other metals. Arch. Microbiol. 159, 336–344 (1993).

    Article  CAS  PubMed  Google Scholar 

  20. Lovley, D. R. et al. Oxidation of aromatic contaminants coupled to microbial iron reduction. Nature 339, 297–300 (1989).

    Article  CAS  Google Scholar 

  21. Lovley, D. R. & Lonergan, D. J. Anaerobic oxidation of toluene, phenol, and para-cresol by the dissimilatory iron-reducing organism, GS-15. Appl. Environ. Microbiol. 56, 1858–1864 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Sung, Y. et al. Geobacter lovleyi sp. nov. strain SZ, a novel metal-reducing and tetrachloroethene-dechlorinating bacterium Appl. Environ. Microbiol. 72, 2775–2782 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Nevin, K. P. et al. Geobacter bemidjiensis sp. nov. and Geobacter psychrophilus sp. nov., two novel Fe(III)-reducing subsurface isolates Int. J. Syst. Evol. Microbiol. 55, 1667–1674 (2005).

    Article  CAS  PubMed  Google Scholar 

  24. Lovley, D. R., Phillips, E. J. P., Gorby, Y. A. & Landa, E. R. Microbial reduction of uranium. Nature 350, 413–416 (1991).

    Article  CAS  Google Scholar 

  25. Ortiz-Bernad, I., Anderson, R. T., Vrionis, H. A. & Lovley, D. R. Vanadium respiration by Geobacter metallireducens: novel strategy for in situ removal of vanadium from groundwater. Appl. Environ. Microbiol. 70, 3091–3095 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lovley, D. R., Coates, J. D., Blunt Harris, E. L., Phillips, E. J. P. & Woodward, J. C. Humic substances as electron acceptors for microbial respiration. Nature 382, 445–448 (1996).

    CAS  Google Scholar 

  27. Lovley, D. R. Dissimilatory metal reduction. Annu. Rev. Microbiol. 47, 263–290 (1993).

    Article  CAS  PubMed  Google Scholar 

  28. Anderson, R. T. et al. Stimulating the in situ activity of Geobacter species to remove uranium from the groundwater of a uranium-contaminated aquifer. Appl. Environ. Microbiol. 69, 5884–5891 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. N'Guessan, A. L., Vrionis, H. A., Resch, C. T., Long, P. E. & Lovley, D. R. Sustained removal of uranium from contaminated groundwater following stimulation of dissimilatory metal reduction. Environ. Sci. Technol. 42, 2999–3004 (2008).

    Article  CAS  PubMed  Google Scholar 

  30. Rooney-Varga, J. N., Anderson, R. T., Fraga, J. L., Ringelberg, D. & Lovley, D. R. Microbial communities associated with anaerobic benzene degradation in a petroleum-contaminated aquifer. Appl. Environ. Microbiol. 65, 3056–3063 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Roling, W. F. M., van Breukelen, B. M., Braster, M., Lin, B. & van Verseveld, H. W. Relationships between microbial community structure and hydrochemistry in a landfill leachate-polluted aquifer. Appl. Environ. Microbiol. 67, 4619–4629 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Botton, S., van Harmelen, M., Braster, M., Parsons, J. R. & Roling, W. F. M. Dominance of Geobacteraceae in BTX-degrading enrichments from an iron-reducing aquifer. FEMS Microbiol. Ecol. 62, 118–130 (2007).

    Article  CAS  PubMed  Google Scholar 

  33. Lovley, D. R., Woodward, J. C. & Chapelle, F. H. Stimulated anoxic biodegradation of aromatic hydrocarbons using Fe(III) ligands. Nature 370, 128–131 (1994).

    Article  CAS  PubMed  Google Scholar 

  34. Lovley, D. R., Woodward, J. C. & Chapelle, F. H. Rapid anaerobic benzene oxidation with a variety of chelated Fe(III) forms. Appl. Environ. Microbiol. 62, 288–291 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Bond, D. R., Holmes, D. E., Tender, L. M. & Lovley, D. R. Electrode-reducing microorganisms that harvest energy from marine sediments. Science 295, 483–485 (2002). The first study to describe microorganisms that are capable of direct extracellular electron transfer to electrodes.

    Article  CAS  PubMed  Google Scholar 

  36. Jung, S. & Regan, J. M. Comparison of anode bacterial communities and performance in microbial fuel cells with different electron donors. Appl. Microbiol. Biotechnol. 77, 393–402 (2007).

    Article  CAS  PubMed  Google Scholar 

  37. Lee, H. S., Parameswaran, P., Kato-Marcus, A., Torres, C. I. & Rittmann, B. E. Evaluation of energy-conversion efficiencies in microbial fuel cells (MFCs) utilizing fermentable and non-fermentable substrates. Water Res. 42, 1501–1510 (2008).

    Article  CAS  PubMed  Google Scholar 

  38. Liu, Y., Harnisch, F., Fricke, K., Sietmann, R. & Schroder, U. Improvement of the anodic bioelectrocatalytic activity of mixed culture biofilms by a simple consecutive electrochemical selection procedure. Biosens. Bioelectron. 24, 1012–1017 (2008).

    Article  CAS  PubMed  Google Scholar 

  39. Nevin, K. P. et al. Power output and columbic efficiencies from biofilms of Geobacter sulfurreducens comparable to mixed community microbial fuel cells. Environ. Microbiol. 10, 2505–2514 (2008).

    Article  CAS  PubMed  Google Scholar 

  40. Yi, H. et al. Selection of a variant of Geobacter sulfurreducens with enhanced capacity for current production in microbial fuel cells. Biosens. Bioelectron. 24, 3498–3503 (2009).

    Article  CAS  PubMed  Google Scholar 

  41. Gregory, K. B., Bond, D. R. & Lovley, D. R. Graphite electrodes as electron donors for anaerobic respiration. Environ. Microbiol. 6, 596–604 (2004).

    Article  CAS  PubMed  Google Scholar 

  42. Gregory, K. B. & Lovley, D. R. Remediation and recovery of uranium from contaminated subsurface environments with electrodes. Environ. Sci. Technol. 39, 8943–8947 (2005).

    Article  CAS  PubMed  Google Scholar 

  43. Strycharz, S. M. et al. Graphite electrode as a sole electron donor for reductive dechlorination of tetrachlorethene by Geobacter lovleyi. Appl. Environ. Microbiol. 74, 5943–5947 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Childers, S. E., Ciufo, S. & Lovley, D. R. Geobacter metallireducens accesses insoluble Fe(III) oxide by chemotaxis. Nature 416, 767–769 (2002).

    Article  CAS  PubMed  Google Scholar 

  45. Lin, W. C., Coppi, M. V. & Lovley, D. R. Geobacter sulfurreducens can grow with oxygen as a terminal electron acceptor. Appl. Environ. Microbiol. 70, 2525–2528 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Methe, B. A. et al. Genome of Geobacter sulfurreducens: metal reduction in subsurface environments. Science 302, 1967–1969 (2003).

    Article  CAS  PubMed  Google Scholar 

  47. Mahadevan, R. et al. Characterization of Metabolism in the Fe(III)-reducing organism Geobacter sulfurreducens by constraint-based modeling. Appl. Environ. Microbiol. 72, 1558–1568 (2006). This group constructed the initial genome-scale metabolic model of G. sulfurreducens that elucidated the role of global proton balance in the energetics of extracellular electron transfer.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lovley, D. R. Dissimilatory Fe(III) and Mn(IV) reduction. Microbiol. Rev. 55, 259–287 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Tang, Y. J. et al. Flux analysis of central metabolic pathways in Geobacter metallireducens during reduction of soluble Fe(III)-nitrilotriacetic acid. Appl. Environ. Microbiol. 73, 3859–3864 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Risso, C., Methe, B. A., Elifantz, H., Holmes, D. E. & Lovley, D. R. Highly conserved genes in Geobacter species with expression patterns indicative of acetate limitation. Microbiology 154, 2589–2599 (2008).

    Article  CAS  PubMed  Google Scholar 

  51. Elifantz, H. et al. Expression of acetate permease-like (apl) genes in subsurface communities of Geobacter species under fluctuating acetate concentrations. FEMS Microbiol. Ecol. 73, 441–449 (2010).

    CAS  PubMed  Google Scholar 

  52. Segura, D., Mahadevan, R., Juarez, K. & Lovley, D. R. Computational and experimental analysis of redundancy in the central metabolism of Geobacter sulfurreducens. PLoS Comput. Biol. 4, e36 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Izallalen, M. et al. Geobacter sulfurreducens strain engineered for increased rates of respiration. Metab. Eng. 10, 267–275 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Butler, J. E. et al. Genomic and microarray analysis of aromatics degradation in Geobacter metallireducens and comparison to a Geobacter isolate from a contaminated field site. BMC Genomics 8, 180 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Sun, J et al. Genome-scale constraint-based modeling of Geobacter metallireducens. BMC Syst. Biol. 3, 15 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Cronan, J. E. & Laporte, D. in Escherichia coli and Salmonella: Cellular and Molecular Biology (ASM Press, Washington, D. C., 1996).

    Google Scholar 

  57. Risso, C., Van Dien, S. J., Orloff, A., Lovley, D. R. & Coppi, M. V. Elucidation of an alternate isoleucine biosynthesis pathway in Geobacter sulfurreducens. J. Bacteriol. 190, 2266–2274 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Mahadevan, R. & Palsson, B. O. Properties of metabolic networks: structure versus function. Biophys. J. 88, L07–L09 (2005).

    Article  CAS  PubMed  Google Scholar 

  59. Mahadevan, R et al. Characterizing regulation of metabolism in Geobacter sulfurreducens through genome-wide expression data and sequence analysis. Omics 12, 33–59 (2008).

    Article  CAS  PubMed  Google Scholar 

  60. Garg, S., Yang, L. & Mahadevan, R. Thermodynamic analysis of regulation in metabolic networks using constraint-based modeling. BMC Res. Notes 3, 125 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Almaas, E., Kovacs, B., Vicsek, T., Oltvai, Z. N. & Barabasi, A. L. Global organization of metabolic fluxes in the bacterium Escherichia coli. Nature 427, 839–843 (2004).

    Article  CAS  PubMed  Google Scholar 

  62. Jeong, H., Tombor, B., Albert, R., Oltvai, Z. N. & Barabasi, A. L. The large-scale organization of metabolic networks. Nature 407, 651–654 (2000).

    Article  CAS  PubMed  Google Scholar 

  63. Alon, U. in An Introduction to Systems Biology (Taylor & Francis Group, Boca Raton, 2007).

    Google Scholar 

  64. Edwards, J. S. & Palsson, B. O. The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities. Proc. Natl Acad. Sci. USA 97, 5528–5533 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Papp, B., Pal, C. & Hurst, L. D. Metabolic network analysis of the causes and evolution of enzyme dispensability in yeast. Nature 429, 661–664 (2004).

    Article  CAS  PubMed  Google Scholar 

  66. Mahadevan, R. & Lovley, D. R. The degree of redundancy in metabolic genes is linked to mode of metabolism. Biophys. J. 94, 1216–1220 (2008).

    Article  CAS  PubMed  Google Scholar 

  67. Reguera, G et al. Extracellular electron transfer via microbial nanowires. Nature 435, 1098–1101 (2005).

    Article  CAS  PubMed  Google Scholar 

  68. Reguera, G. et al. Biofilm and nanowire production leads to increased current in Geobacter sulfurreducens fuel cells. Appl. Environ. Microbiol. 72, 7345–7348 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Lovley, D. R. Bug juice: harvesting electricity with microorganisms. Nature Rev. Microbiol. 4, 497–508 (2006).

    Article  CAS  Google Scholar 

  70. Esteve-Nunez, A., Sosnik, J., Visconti, P. & Lovley, D. R. Fluorescent properties of c-type cytochromes reveal their potential role as an extracytoplasmic electron sink in Geobacter sulfurreducens. Environ. Microbiol. 10, 497–505 (2008).

    Article  CAS  PubMed  Google Scholar 

  71. Leang, C., Qian, X., Mester, T. & Lovley, D. R. Alignment of the c-type cytochrome OmcS along pili of Geobacter sulfurreducens. Appl. Environ. Microbiol. 76, 4080–4084 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Nevin, K. P. et al. Anode biofilm transcriptomics reveals outer surface components essential for high density current production in Geobacter sulfurreducens fuel cells. PLoS ONE 4, e5628 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Inoue, K. et al. Purification and characterization of OmcZ, an outer-surface, octaheme c-type cytochrome essential for optimal current production by Geobacter sulfurreducens. Appl. Environ. Microbiol. 76, 3999–4007 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Esteve-Nunez, A., Rothermich, A., Sharma, M. & Lovley, D. R. Growth of Geobacter sulfurreducens under nutrient-limiting conditions in continuous culture. Environ. Microbiol. 7, 641–648 (2005).

    Article  CAS  PubMed  Google Scholar 

  75. Srinivasan, K. & Mahadevan, R. Characterization of proton production and consumption associated with microbial metabolism. BMC Biotechnol. 10, 2 (2010).

  76. Lovley, D. R. Extracellular electron transfer: wires, capacitors, iron lungs, and more. Geobiology 6, 225–231 (2008).

    Article  CAS  PubMed  Google Scholar 

  77. Nevin, K. P. & Lovley, D. R. Lack of production of electron-shuttling compounds or solubilization of Fe(III) during reduction of insoluble Fe(III) oxide by Geobacter metallireducens. Appl. Environ. Microbiol. 66, 2248–2251 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Bond, D. R. & Lovley, D. R. Electricity production by Geobacter sulfurreducens attached to electrodes. Appl. Environ. Microbiol. 69, 1548–1555 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Marsili, E. et al. Shewanella secretes flavins that mediate extracellular electron transfer. Proc. Natl Acad. Sci. USA 105, 3968–3973 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Richter, H. et al. Electricity generation by Geobacter sulfurreducens attached to gold electrodes. Langmuir 24, 4376–4379 (2008).

    Article  CAS  PubMed  Google Scholar 

  81. Nevin, K. P. & Lovley, D. R. Mechanisms for accessing insoluble Fe(III) oxide during dissimilatory Fe(III) reduction by Geothrix fermentans. Appl. Environ. Microbiol. 68, 2294–2299 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Nevin, K. P. & Lovley, D. R. Mechanisms for Fe(III) oxide reduction in sedimentary environments. Geomicrobiol. J. 19, 141–159 (2002).

    Article  CAS  Google Scholar 

  83. Bond, D. R. & Lovley, D. R. Evidence for involvement of an electron shuttle in electricity generation by Geothrix fermentans. Appl. Environ. Microbiol. 71, 2186–2189 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Newman, D. K. & Kolter, R. A role for excreted quinones in extracellular electron transfer. Nature 405, 94–97 (2000).

    Article  CAS  PubMed  Google Scholar 

  85. Lovley, D. R. The microbe electric: conversion of organic matter to electricity. Curr. Opin. Biotechnol. 19, 564–571 (2008).

    Article  CAS  PubMed  Google Scholar 

  86. Burgard, A. P., Pharkya, P. & Maranas, C. D. OptKnock: a bilevel programming framework for identifying gene knockout strategies for microbial strain optimization. Biotechnol. Bioeng. 84, 647–657 (2003).

    Article  CAS  PubMed  Google Scholar 

  87. Fong, S. S. et al. In silico design and adaptive evolution of Escherichia coli for production of lactic acid. Biotechnol. Bioeng. 91, 643–648 (2005).

    Article  CAS  PubMed  Google Scholar 

  88. Holmes, D. E., Finneran, K. T., O'Neil, R. A. & Lovley, D. R. Enrichment of members of the family Geobacteraceae associated with stimulation of dissimilatory metal reduction in uranium- contaminated aquifer sediments. Appl. Environ. Microbiol. 68, 2300–2306 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Holmes, D. E. et al. Subsurface clade of Geobacteraceae that predominates in a diversity of Fe(III)-reducing subsurface environments. ISME J. 1, 663–677 (2007).

    Article  CAS  PubMed  Google Scholar 

  90. Mouser, P. J. et al. Influence of heterogeneous ammonium availability on bacterial community structure and the expression of nitrogen fixation and ammonium transporter genes during in situ bioremediation of uranium-contaminated groundwater. Environ. Sci. Technol. 43, 4386–4392 (2009).

    Article  CAS  PubMed  Google Scholar 

  91. Risso, C. et al. Genome-scale comparison and constraint-based metabolic reconstruction of the facultative anaerobic Fe(III)-reducer Rhodoferax ferrireducens. BMC Genomics 10, 447 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Zhuang, K. et al. D. Genome-scale dynamic modeling of the competition between Rhodoferax and Geobacter in anoxic subsurface environments. ISME J. 29 Jul 2010 (doi: 10.1038/ismej.2010.117). The first genome-scale dynamic multispecies model to accurately predict the outcome of competition among Fe III reducers under varying acetate and ammonium availabilities.

  93. Methe, B. A., Webster, J., Nevin, K. P. & Lovley, D. R. DNA microarray analysis of nitrogen fixation and Fe(III) reduction in Geobacter sulfurreducens. Appl. Environ. Microbiol. 71, 2530–2538 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Steefel, C. I., DePaolo, D. J. & Lichtner, P. C. Reactive transport modeling: An essential tool and a new research approach for the Earth sciences. Earth Planet. Sci. Lett. 240, 539–558 (2005).

    Article  CAS  Google Scholar 

  95. Scheibe, T. D. et al. Coupling a genome-scale metabolic model with a reactive transport model to describe in situ uranium bioremediation. Microb. Biotechnol. 2, 274–286 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Zhao, J., Fang, Y., Scheibe, T. D., Lovley, D. R. & Mahadevan, R. Modeling and sensitivity analysis of electron capacitance for Geobacter in sedimentary environments. J. Contam. Hydrol. 112, 30–44 (2010).

    Article  CAS  PubMed  Google Scholar 

  97. Fennell, D. E., Carroll, A. B., Gossett, J. M. & Zinder, S. H. Assessment of indigenous reductive dechlorinating potential at a TCE-contaminated site using microcosms, polymerase chain reaction analysis, and site data. Environ. Sci. Technol. 35, 1830–1839 (2001).

    Article  CAS  PubMed  Google Scholar 

  98. Lee, P. K., Macbeth, T. W., Sorenson, K. S. Jr, Deeb, R. A. & Alvarez-Cohen, L. Quantifying genes and transcripts to assess the in situ physiology of “Dehalococcoides” spp. in a trichloroethene-contaminated groundwater site. Appl. Environ. Microbiol. 74, 2728–2739 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Griffin, B. M., Tiedje, J. M. & Loffler, F. E. Anaerobic microbial reductive dechlorination of tetrachloroethene to predominately trans-1,2-dichloroethene. Environ. Sci. Technol. 38, 4300–4303 (2004).

    Article  CAS  PubMed  Google Scholar 

  100. Major, D. W. et al. Field demonstration of successful bioaugmentation to achieve dechlorination of tetrachloroethene to ethene. Environ. Sci. Technol. 36, 5106–5116 (2002).

    Article  CAS  PubMed  Google Scholar 

  101. Islam, A., Edwards, E. A. & Mahadevan, R. Characterizing the metabolism of Dehalococcoides with a constraint-based model. PLoS Comput. Biol. 6, e1000887 (2010).

    Article  CAS  Google Scholar 

  102. Henry, C. S. et al. High-throughput generation, optimization and analysis of genome-scale metabolic models. Nature Biotech. 28, 977–982 (2010). This article details an automated, web-based pipeline for building genome-scale models. The pipeline was used to develop 130 models of taxonomically diverse bacteria.

    Article  CAS  Google Scholar 

  103. Zengler, K. et al. Cultivating the uncultured. Proc. Natl Acad. Sci. USA 99, 15681–15686 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Rappe, M. S. & Giovannoni, S. J. The uncultured microbial majority. Annu. Rev. Microbiol. 57, 369–394 (2003).

    Article  CAS  PubMed  Google Scholar 

  105. Ishoey, T., Woyke, T., Stepanauskas, R., Novotny, M. & Lasken, R. S. Genomic sequencing of single microbial cells from environmental samples. Curr. Opin. Microbiol. 11, 198–204 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Lasken, R. S. Genomic DNA amplification by the multiple displacement amplification (MDA) method. Biochem. Soc. Trans. 37, 450–453 (2009).

    Article  CAS  PubMed  Google Scholar 

  107. Stolyar, S. et al. Metabolic modeling of a mutualistic microbial community. Mol. Syst. Biol. 3, 92 (2007). The first multispecies model of syntrophic interactions in a microbial community, involving hydrogen transfer between a sulphate-reducing bacterium and a methanogen. Modelling of the central metabolism of the two organisms showed the ability of models to predict the steady-state microbial composition of a community.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Salimi, F., Zhuang, K. & Mahadevan, R. Genome-scale modeling of a clostridial co-culture for consolidated bioprocessing. Biotechnol. J. 5, 726–738 (2010).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge the US Department of Energy's Genomic Science Program (cooperative agreement DE-FC02-02ER63446) and Subsurface Biogeochemical Research Program (grant DE-FG02-07ER64367) for funding, and C. O'Connell for help with the illustrations.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Radhakrishnan Mahadevan.

Ethics declarations

Competing interests

Bernhard Ø. Palsson has a financial interest in Genomatica Inc., although the findings reported in this publication do not directly relate to the interests of Genomatica, Inc.

Radhakrishnan Mahadevan and Derek R. Lovely declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Radhakrishnan Mahadevan's homepage

Updated list of COBRA reconstructions

Glossary

Humic substances

The fraction of the dark organic matter that is stable and can serve as electron carriers.

Anoxic submerged soil

Oxygen-depleted sediment.

Aquifer

An underground, water-saturated, permeable sediment.

Dissimilatory metal reduction

An enzymatic reaction in which a metal is reduced but is not assimilated or incorporated into cells for the purposes of biosynthesis during, for example, respiration.

Tricarboxylic acid cycle

The reaction cycle that serves as the primary source of reduced carriers in metabolism.

ACK–POR pathway

The acetate kinase (ACK)–pyuvate oxidoreductase (POR) pathway for the generation of pyruvate from acetate in anaerobes.

Anapleurotic reaction

A reaction that replenishes metabolites that are removed from the tricarboxylic acid cycle.

Glyoxylate bypass

An alternative pathway (instead of the tricarboxylic acid cycle) for the use of acetate through the generation of glyoxalate.

Metabolite connectivity

The number of reactions in which a metabolite participates.

ATP synthase

An enzyme that synthesizes ATP using the electrochemical gradient across the membrane.

OptKnock

A model-based optimization algorithm for metabolic engineering.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mahadevan, R., Palsson, B. & Lovley, D. In situ to in silico and back: elucidating the physiology and ecology of Geobacter spp. using genome-scale modelling. Nat Rev Microbiol 9, 39–50 (2011). https://doi.org/10.1038/nrmicro2456

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro2456

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing