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.

  • Outlook
  • Published:

Metagenomics and industrial applications

Nature Reviews Microbiology volume 3, pages 510–516 (2005)Cite this article

Abstract

Different industries have different motivations to probe the enormous resource that is uncultivated microbial diversity. Currently, there is a global political drive to promote white (industrial) biotechnology as a central feature of the sustainable economic future of modern industrialized societies. This requires the development of novel enzymes, processes, products and applications. Metagenomics promises to provide new molecules with diverse functions, but ultimately, expression systems are required for any new enzymes and bioactive molecules to become an economic success. This review highlights industrial efforts and achievements in metagenomics.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Multi-parameter footprint analysis.
Figure 2: Industrial enzymes — from the metagenome to applications and processes.

Similar content being viewed by others

References

  1. Handelsman, J. Metagenomics: application of genomics to uncultured microorganisms. Microbiol. Mol. Biol. Rev. 68, 669–685 (2004).

    Article  CAS  Google Scholar 

  2. Torsvik, V., Ovreas, L. & Thingstad, T. F. Prokaryotic diversity-magnitude, dynamics, and controlling factors. Science 296, 1064–1066 (2002).

    Article  CAS  Google Scholar 

  3. Venter, J. C. et al. Environmental genome shotgun sequencing of the Sargasso Sea. Science 304, 66–74 (2004).

    Article  CAS  Google Scholar 

  4. Curtis, T. P., Sloan, W. T. & Scannell J. W. Estimating prokaryotic diversity and its limits. Proc. Natl Acad. Sci. USA 99, 10494–10499 (2002).

    Article  CAS  Google Scholar 

  5. Ward, B. B. How many species of prokaryotes are there? Proc. Natl Acad. Sci. USA 99, 10234–10236 (2002).

    Article  CAS  Google Scholar 

  6. Schloss, P. D. & Handelsman, J. Status of the microbial census. Microbiol. Mol. Biol. Rev. 68, 686–691 (2004).

    Article  Google Scholar 

  7. Burton, S. G., Cowan, D. A. & Woodley J. M. The search for the ideal biocatalyst. Nature Biotechnol. 20, 37–45 (2002).

    Article  CAS  Google Scholar 

  8. Maurer, K. H. Detergent proteases. Curr. Opin. Biotechnol. 15, 330–334 (2004).

    Article  CAS  Google Scholar 

  9. Homann, M. J. et al. Rapid identification of enantioselective ketone reductions using targeted microbial libraries. Tetrahedron 60, 789–797 (2004).

    Article  CAS  Google Scholar 

  10. Piel, J. Metabolites from symbiotic bacteria. Nat. Prod. Rep. 21, 519–538 (2004).

    Article  CAS  Google Scholar 

  11. 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  Google Scholar 

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

    Article  CAS  Google Scholar 

  13. Kirk, O., Borchert, T. V. & Fuglsang C. C. Industrial enzyme applications. Curr. Opin. Biotechnol. 13, 345–351 (2002).

    Article  CAS  Google Scholar 

  14. Patel, R. N. et al. Enzymic preparation of (3R-cis)-3-(acetyloxy)-4-phenyl-2-azetidinone: a taxol side-chain synthon. Biotechnol. Appl. Biochem. 20, 23–33 (1994).

    CAS  PubMed  Google Scholar 

  15. Global Industry Analysts. Industrial enzymes — a global multi-client market research project. (GIA, San José, California, USA, 2004).

  16. The application of biotechnology to industrial sustainability. (Organisation for economic co-operation and development (OECD), 2001).

  17. Schepens, H. et al. White Biotechnology: gateway to a more sustainable future [online] <www.mckinsey.com/clientservice/chemicals/pdf/BioVision_Booklet_final.pdf> (2003).

    Google Scholar 

  18. Riese, J. Surfing the third wave: new value chain creation opportunities in industrial biotechnology (McKinsey & Company, Frankfurt, Germany, 2003).

    Google Scholar 

  19. DSM Position Document, Industrial (white) biotechnology: an effective route to increase EU innovation and sustainable growth [online] <http://www.b-basic.nl/documents/DSMIndustrial-white-biotechnology.pdf> (2004).

  20. Herrera, S. Industrial biotechnology — a chance at redemption. Nature Biotechnol. 22, 671–675 (2004).

    Article  CAS  Google Scholar 

  21. Schoemaker, H. E., Mink, D. & Wubbolts, M. G. Dispelling the myths — biocatalysis in industrial synthesis. Science 299, 1694–1697 (2003).

    Article  CAS  Google Scholar 

  22. Schmid, A. et al. Industrial biocatalysis today and tomorrow. Nature 409, 258–268 (2001).

    Article  CAS  Google Scholar 

  23. Schmid, A., Hollmann, F., Park, J. B. & Buhler, B. The use of enzymes in the chemical industry in Europe. Curr. Opin. Biotechnol. 13, 359–366 (2002).

    Article  CAS  Google Scholar 

  24. Straathof, A. J., Panke, S. & Schmid, A. The production of fine chemicals by biotransformations. Curr. Opin. Biotechnol. 13, 548–556 (2002).

    Article  CAS  Google Scholar 

  25. Roberts S. M. Biocatalysts in synthetic organic chemistry. Tetrahedron 60, 499–500 (2004).

    Article  CAS  Google Scholar 

  26. Lorenz, P., Liebeton, K., Niehaus, F. &, Eck, J. Screening for novel enzymes for biocatalytic processes: accessing the metagenome as a resource of novel functional sequence space. Curr. Opin. Biotechnol. 13, 572–577 (2002).

    Article  CAS  Google Scholar 

  27. Schloss, P. D. & Handelsman, J. Biotechnological prospects from metagenomics. Curr. Opin. Biotechnol. 14, 303–310 (2003).

    Article  CAS  Google Scholar 

  28. Torsvik V. L. & Goksoyr J. Determination of bacterial DNA in soil. Soil Biol. Biochem. 10, 7–12 (1980).

    Article  Google Scholar 

  29. Pace, N. R., Stahl, D. A., Lane, D. J. & Olsen, G. J. The analysis of natural microbial populations by ribosomal RNA sequences. Adv. Microbial Ecol. 9, 1–55 (1986).

    Article  CAS  Google Scholar 

  30. Schmidt, T. M., DeLong, E. F. & Pace, N. R. Analysis of a marine picoplankton community by 16S rRNA gene cloning and sequencing. J. Bacteriol. 173, 4371–4378 (1991).

    Article  CAS  Google Scholar 

  31. Healy, F. G. et al. Direct isolation of functional genes encoding cellulases from the microbial consortia in a thermophilic, anaerobic digester maintained on lignocellulose. Appl. Microbiol. Biotechnol. 43, 667–674 (1995).

    Article  CAS  Google Scholar 

  32. Staley, J. T. & Konopka, A. Measurement of in situ activities of nonphotosynthetic microorganisms in aquatic and terrestrial habitats. Annu. Rev. Microbiol. 39, 321–346 (1985).

    Article  CAS  Google Scholar 

  33. Short, J. M. & Mathur, E. J. Production and use of normalized DNA libraries. US Patent 5,763,239 (1998).

  34. Radomski, C. C. A., Seow, K. T., Warren, R. A. J. & Yap, W. H. Method for isolating xylanase gene sequences from soil DNA, compositions useful in such method and compositions obtained thereby. US Patent US 5,849,491 (1998).

  35. Robertson, D. E. et al. Exploring nitrilase sequence space for enantioselective catalysis. Appl. Environ. Microbiol. 70, 2429–2436 (2004).

    Article  CAS  Google Scholar 

  36. DeSantis, G. et al. An enzyme library approach to biocatalysis: development of nitrilases for enantioselective production of carboxylic acid derivatives. J. Am. Chem. Soc. 124, 9024–9025 (2002).

    Article  CAS  Google Scholar 

  37. Short, J. M. & Keller, M. Method of high-throughput screening of an environmental library. US Patent 6,806,048 (2004).

  38. Knietsch, A., Bowien, S., Whited, G., Gottschalk, G. & Daniel, R. Identification and characterization of coenzyme B12-dependent glycerol dehydratase- and diol dehydratase-encoding genes from metagenomic DNA libraries derived from enrichment cultures. Appl. Environ. Microbiol. 69, 3048–3060 (2003).

    Article  CAS  Google Scholar 

  39. Breves, R., Maurer, K. H., Eck, J., Lorenz P. & Zinke H. New glycosyl hydrolases. PCT patent application WO 03/054177 (2003).

  40. iebeton K. & Eck J. Identification and expression in E. coli of novel nitrile hydratases from the metagenome. Eng. Life Sci. 4, 554–562 (2004).

    Google Scholar 

  41. Hobel, C. F. V. et al. Use of low nutrient enrichment to access novel amylase genes in silent diversity of thermophiles. World J. Microbiol. Biotechnol. 20, 801–809 (2004).

    Article  CAS  Google Scholar 

  42. Gray, K. A., Richardson, T. H., Robertson, D. E., Swanson, P. E. & Subramanian, M. V. Soil-based gene discovery: a new technology to accelerate and broaden biocatalytic applications. Adv. Appl. Microbiol. 52, 1–27 (2003).

    Article  CAS  Google Scholar 

  43. Detter, J. C. et al. Isothermal strand-displacement amplification applications for high-throughput genomics. Genomics 80, 691–698 (2002).

    Article  CAS  Google Scholar 

  44. McDonald, A. E. & Vanlerberghe, G. C. Alternative oxidase and plastoquinol terminal oxidase in marine prokaryotes of the Sargasso Sea. Gene 349, 15–24 (2005).

    Article  CAS  Google Scholar 

  45. Uchiyama, T., Abe, T., Ikemura, T. & Watanabe, K. Substrate-induced gene-expression screening of environmental metagenome libraries for isolation of catabolic genes. Nature Biotechnol. 23, 88–93 (2004).

    Article  Google Scholar 

  46. Service, R. F. Surviving the blockbuster syndrome. Science 303, 1796–1799 (2004).

    Article  Google Scholar 

  47. Leeb M. A shot in the arm. Nature 431, 892–893 (2004).

    Article  CAS  Google Scholar 

  48. Cragg, G. M. & Newman, D. J. Medicinals for the millennia: the historical record. Ann. N. Y. Acad. Sci. 953, 3–25 (2001).

    Article  CAS  Google Scholar 

  49. Newman, D. J., Cragg, G. M. & Snader, K. M. Natural products as sources of new drugs over the period 1981–2002. J. Nat. Prod. 66, 1022–1037 (2003).

    Article  CAS  Google Scholar 

  50. Osburne, M. S., Grossman, T. H., August, P. R. & MacNeil, I. A. Tapping into microbial diversity for natural products drug discovery. ASM News 66, 411–417 (2000).

    Google Scholar 

  51. Daniel, R. The soil metagenome — a rich resource for the discovery of novel natural products. Curr. Opin. Biotechnol. 15 199–204 (2004).

    Article  CAS  Google Scholar 

  52. Seow, K. T. et al. A study of iterative type II polyketide synthases, using bacterial genes cloned from soil DNA: a means to access and use genes from uncultured microorganisms. J. Bacteriol. 179, 7360–7368 (1997).

    Article  CAS  Google Scholar 

  53. Wang, G. Y. et al. Novel natural products from soil DNA libraries in a streptomycete host. Org. Lett. 2, 2401–2404 (2000).

    Article  CAS  Google Scholar 

  54. Pfeifer, B. A., Admiraal, S. J., Gramajo, H., Cane, D. E. & Khosla, C. Biosynthesis of complex polyketides in a metabolically engineered strain of E. coli. Science 291, 1790–1792 (2001).

    Article  CAS  Google Scholar 

  55. Courtois, S. et al. Recombinant environmental libraries provide access to microbial diversity for drug discovery from natural products. Appl. Environ. Microbiol. 69, 49–55 (2003).

    Article  CAS  Google Scholar 

  56. MacNeil, I. A. et al. Expression and isolation of antimicrobial small molecules from soil DNA libraries. J. Mol. Microbiol. Biotechnol. 3, 301–308 (2001).

    CAS  PubMed  Google Scholar 

  57. Martinez, A. et al. Genetically modified bacterial strains and novel bacterial artificial chromosome shuttle vectors for constructing environmental libraries and detecting heterologous natural products in multiple expression hosts. Appl. Environ. Microbiol. 70, 2452–2463 (2004).

    Article  CAS  Google Scholar 

  58. Quaiser, A. et al. First insight into the genome of an uncultivated crenarchaeote from soil. Environ. Microbiol. 4, 603–611 (2002).

    Article  CAS  Google Scholar 

  59. Berry, A. E., Chiocchini, C., Selby, T., Sosio, M. & Wellington E. M. Isolation of high molecular weight DNA from soil for cloning into BAC vectors. FEMS Microbiol. Lett. 223, 15–20 (2003).

    Article  CAS  Google Scholar 

  60. Short, J. Screening for novel bioactivities. US Patent US 6,057,103 (2000).

  61. Piel, J. et al. Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei. Proc. Natl Acad. Sci. USA 101, 16222–16227 (2004).

    Article  CAS  Google Scholar 

  62. Richardson, T. H. et al. A novel, high performance enzyme for starch liquefaction. Discovery and optimization of a low pH, thermostable α-amylase J. Biol. Chem. 277, 26501–26507 (2002).

    Article  CAS  Google Scholar 

  63. Henne, A., Schmitz, R. A., Bömeke, M., Gottschalk, G. & Daniel, R. Screening of environmental DNA libraries for the presence of genes conferring lipolytic activity on Escherichia coli. Appl. Environ. Microbiol. 66, 3113–3116 (2000).

    Article  CAS  Google Scholar 

  64. Rondon, M. R. et al. Cloning the soil metagenome: a strategy for accessing the genetic and functional diversity of uncultured microorganisms. Appl. Environ. Microbiol. 66, 2541–2547 (2000).

    Article  CAS  Google Scholar 

  65. Knietsch, A., Waschkowitz, T., Bowien, S., Henne, A. & Daniel, R. Metagenomes of complex microbial consortia derived from different soils as sources for novel genes conferring formation of carbonyls from short-chain polyols on Escherichia coli. J. Mol. Microbiol. Biotechnol. 5, 46–56 (2003).

    Article  CAS  Google Scholar 

  66. Knietsch, A., Waschkowitz, T., Bowien, S., Henne, A. & Daniel, R. Construction and screening of metagenomic libraries derived from enrichment cultures: generation of a gene bank for genes conferring alcohol oxidoreductase activity on Escherichia coli. Appl. Environ. Microbiol. 69, 1408–1416 (2003).

    Article  CAS  Google Scholar 

  67. Gabor, E. M., de Vries, E. J. & Janssen, D. B. Construction, characterization, and use of small-insert gene banks of DNA isolated from soil and enrichment cultures for the recovery of novel amidases. Environ. Microbiol. 6, 948–958 (2004).

    Article  CAS  Google Scholar 

  68. Gabor, E. M. Harvesting novel biocatalysts from the metagenome. Thesis, Univ. Groningen (2004).

    Google Scholar 

  69. Entcheva, P., Liebl, W., Johann, A., Hartsch, T. & Streit, W. R. Direct cloning from enrichment cultures, a reliable strategy for isolation of complete operons and genes from microbial consortia. Appl. Environ. Microbiol. 67, 89–99 (2001).

    Article  CAS  Google Scholar 

  70. Gupta, R., Beg, Q. K. & Lorenz, P. Bacterial alkaline proteases: molecular approaches and industrial applications. Appl. Microbiol. Biotechnol. 59, 15–32 (2002).

    Article  CAS  Google Scholar 

  71. Rees, H. C., Grant, S., Jones, B., Grant, W. D. & Heaphy, S. Detecting cellulase and esterase enzyme activities encoded by novel genes present in environmental DNA libraries. Extremophiles 7, 415–421 (2003).

    Article  CAS  Google Scholar 

  72. Cottrell, M. T., Moore, J. A. & Kirchman, D. L. Chitinases from uncultured marine microorganisms. Appl. Environ. Microbiol. 65, 2553–2557 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Henne, A., Daniel, R., Schmitz, R. A. & Gottschalk, G. Construction of environmental DNA libraries in Escherichia coli and screening for the presence of genes conferring utilization of 4-hydroxybutyrate. Appl. Environ. Microbiol. 65, 3901–3907 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Gillespie, D. E. et al. Isolation of antibiotics turbomycin A and B from a metagenomic library of soil microbial DNA. Appl. Environ. Microbiol. 68, 4301–4306 (2002).

    Article  CAS  Google Scholar 

  75. Brady, S. F., Chao, C. J. & Clardy, J. Long-chain N-acyltyrosine synthases from environmental DNA. Appl. Environ. Microbiol. 70, 6865–6870 (2004).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank our collegues at BRAIN AG and particularly C. Schleper of the University of Bergen, Norway, and the Zentrum für Evolutionsforschung und Biotechnologie (ZEB), Darmstadt, Germany, for fruitful discussions and sharing ideas and resources.

Author information

Authors and Affiliations

  1. BRAIN AG, Darmstaedterstrasse 34, Zwingenberg, 64673, Germany

    Patrick Lorenz & Jürgen Eck

Authors
  1. Patrick Lorenz
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Jürgen Eck
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Patrick Lorenz.

Ethics declarations

Competing interests

Both authors are senior managers at BRAIN AG.

Related links

Related links

FURTHER INFORMATION

ActivBiotics

Aventis Pharmaceuticals

BRAIN AG

Cubist Pharmaceuticals

EuropaBio

The European Chemical Industry Council

The European Technology Platform for Sustainable Chemistry

Degussa

Diversa

Genencor International

Henkel

Lucigen

Prokaria

Vicuron Pharmaceuticals

Glossary

CONSORTIUM

Physical association between cells of two or more types of microorganisms. Such an association might be advantageous to at least one of the microorganisms.

ENANTIOSELECTIVE

Selection of a particular enantiomer, one of a pair of stereospecific isomers.

GREEN BIOTECHNOLOGY

Biotechnology applied to agriculture, for example, production of transgenic crop plants with genetically engineered improved pest resistance.

RED BIOTECHNOLOGY

Biotechnology in health care that uses substances produced in the human body to fight disease — medicines, vaccines, diagnostics and gene therapy.

REGIOSELECTIVE

Selection of a change that occurs with a greater frequency at one site than at several other sites, usually involving a structural or positional isomer.

SYNTHON

A molecule used as a chemical building block to synthesize complex compounds.

WHITE BIOTECHNOLOGY

Industrial use of biotechnology, for example, to produce fine chemicals, biofuel, bioplastics, enzymes for use in detergents, food and feed. The boundaries between white, green and red biotechnology are blurred.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lorenz, P., Eck, J. Metagenomics and industrial applications. Nat Rev Microbiol 3, 510–516 (2005). https://doi.org/10.1038/nrmicro1161

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro1161

Search

Advanced 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