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Surface–Active Compounds from Microorganisms

Bio/Technology volume 10, pages 60–65 (1992)Cite this article

Abstract

Microbial surfactants are a structurally diverse group of compounds consisting of hydrophilic and hydrophobic domains and which partition preferentially at interfaces. Biosurfactants are of increasing interest commercially as substitutes for synthetic surfactants particularly for environmental applications. This article discusses recent progress in the genetic and biochemical analysis of biosurfactant synthesis as well as the current status of fermentation technologies.

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References

  1. Israelachvili, J.N. 1985. Intermolecular and Surface Forces. Academic Press, NY.

    Google Scholar 

  2. Scriven, L.E. 1976. Equilibrium bi-continuous structures. In: Micellization, Solubilization, and Microemulsions. Mittal, K.L. (Ed.). Plenum Press, NY .

    Google Scholar 

  3. Cooper, D.G.,1986. Biosurfactants Microbiol. Sci. 3: 145–149.

    CAS  PubMed  Google Scholar 

  4. Haferburg, D., Hommel, R., Claus, R. and Kleber, H.-P. 1986. Extracellular microbial lipids as biosurfactants. Advanc. Biochem. Eng. Biotechnol. 33: 54–93.

    Google Scholar 

  5. Cooper, D.G. and Zajic, J.E. 1980. Surface-active compounds from microorganisms. Adv. Appl. Microbiol. 26: 229–253.

    Article  CAS  Google Scholar 

  6. Horbett, T.A. 1988. Molecular origins of the surface activity of proteins. Protein Eng. 2: 172–174.

    Article  CAS  PubMed  Google Scholar 

  7. Ramsay, B., McCarthy, J., Guerra-Santos, L., Käppeli, O., Feichter, A. and Margaritis, A. 1988. Biosurfactant production and diauxic growth of Rhodococcus aurantiacus when using n-alkanes as the carbon cource. Can. J. Microbiol. 34: 1209–1212.

    Article  CAS  Google Scholar 

  8. Finnerty, W.R. and Singer, M.E. 1984. A microbial biosurfactant— physiology, biochemistry, and applications. Dev. Ind. Microbiol. 25: 31–46.

    CAS  Google Scholar 

  9. Hommel, R., Stüwer, O., Stuber, W., Haferburg, D. and Kleber, H.-P. 1987. Production of water-soluble surface-active exolipids by Torulopsis apicola . Appl. Microbiol. Biotechnol. 26: 199–205.

    Article  CAS  Google Scholar 

  10. Kim, J.-S., Powalla, M., Lang, S., Wagner, F., Lunsdorf, H. and Wray, V. 1990. Microbial glycolipid production under nitrogen limitation and resting cell conditions. J. Biotechnol. 13: 257–266.

    Article  CAS  PubMed  Google Scholar 

  11. Guerra-Santos, L.H., Kappeli, O. and Fiechter, A. 1986. Dependence of Pseudomonas aeruginosa continuous culture biosurfactant production on nutritional and environmental factors. Appl. Microbiol. Biotechnol. 24: 443–448.

    Article  CAS  Google Scholar 

  12. Reiling, H.E., Thanei-Wyss, U., Guerra-Santos, L.H., Hirt, R., Kappeli, O. and Fiechter, A. 1986. Pilot plant production of rhamnolipid biosurfactant by Pseudomonas aeruginosa . Appl. Environ. Microbiol. 51: 985–989.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Robert, M., Mercadé, M.E., Bosch, M.P., Parra, J.L., Espuny, M.J., Manresa, M.A. and Guinea, J. 1989. Effect of the carbon source on biosurfactant production by Pseudomonas aeruginosa 44T1. Biotechnol. Lett. 11: 871–874.

    Article  CAS  Google Scholar 

  14. Matsuyama, T., Kaneda, K., Ishizuka, I., Toida, T. and Yano, I. 1990. Surface-active novel glycolipid and linked 3-hydroxy fatty acids produced by Serratia rubidaea . J. Bacteriol. 172: 3015–3022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cooper, D.G. and Paddock, D.A. 1984. Production of a biosurfactant from Torulopsis bombicola . Appl. Environ. Microbiol. 47: 173–176.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Göbbert, U., Lang, S. and Wagner, F. 1984. Sophorose lipid formation by resting cells of Torulopsis bombicola . Biotechnol. Lett. 6: 225–230.

    Article  Google Scholar 

  17. Asmer, H.-J., Lang, S., Wagner, F. and Wray, V. 1988. Microbial production, structure elucidation and bioconversion of sophorose lipids. J. Amer. Oil Chem. Soc. 65: 1460–1466.

    Article  CAS  Google Scholar 

  18. Rapp, P., Bock, H., Wray, V. and Wagner, F., 1979. rmation, isolation and characterization of trehalose dimycolates from Rhodococcus eryihropotis grown on n-alkane. J. Gen. Microbiol. 115: 491–503.

    Article  CAS  Google Scholar 

  19. Powalla, M., Lang, S. and Wray, V. 1989. Penta- and disaccharide lipid formation by Nocardia corynebacteroidesgrown on n-alkanes. Appl. Microbiol. Biotechnol. 31: 473–479.

    Article  CAS  Google Scholar 

  20. Jenneman, G.E., McInerney, M.J., Knapp, R.M., Clark, J.B., Ferro, J.M., Revus, D.E. and Menzie, D.E. 1983. A halotolerant, biosurfactant-producing Bacillus species potentially useful for enhanced oil recovery. Dev. Ind. Microbiol. 24: 485–492.

    CAS  Google Scholar 

  21. Javaheri, M., Jenneman, G.E., McInerney, M.J. and Knapp, R.M. 1985. Anaerobic production of a biosurfactant by Bacillus licheniformis JF-2 Appl. Environ. Microbiol. 50: 698–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. McInerney, M.J., Javaheri, M. and Nagle, D.P. 1990. Properties of the biosurfactant produced by Bacillus licheniformis strain JF-2. J. Ind. Microbiol. 5: 95–102.

    Article  CAS  PubMed  Google Scholar 

  23. Lin, S.C., Goursaud, J.-C., Kramer, P.J., Georgiou, G. and Sharma, M.M. 1990. Production of biosurfactant by Bacillus licheniformis strain JF-2. In: Microbial Enhancement of Oil Recovery—Recent Advances. Donaldson, E. C. (Ed.). Elsevier Science Publishers, Amsterdam.

    Google Scholar 

  24. Horowitz, S., Gilbert, J.N. and Griffin, W.M. 1990. Isolation and characterization of a surfactant produced by Bacillus licheniformis 86. J. Ind. Microbiol. 6: 243–248.

    Article  CAS  Google Scholar 

  25. Neu, T.R., Hartner, T. and Poralla, K. 1990. Surface active properties of viscosin: a peptidolipid antibiotic. Appl. Microbiol. Biotechnol. 32: 518–520.

    CAS  Google Scholar 

  26. Matsuyama, T., Fujita, M. and Yano, I. 1985. Wetting agent produced by Serratia marcescens . FEMS Microbiol. Lett. 28: 125–129.

    Article  CAS  Google Scholar 

  27. Matsuyama, T., Murakami, T., Fujita, M., Fujita, S. and Yano, I. 1986. Extracellular vesicle formation and biosurfactant production by Serratia marcescens . J. Gen. Microbiol. 132: 865–875.

    CAS  Google Scholar 

  28. Arima, K., Kakinuma, A. and Tamura, G., 1968. rfactin, a crystalline peptidelipid surfactant produced by Bacillus subtilis: isolation, characterization and its inhibition of fibrin clot formation Biochem. Biophys. Res. Com. 31: 488–494.

    Article  CAS  PubMed  Google Scholar 

  29. Cooper, D.G., MacDonald, C.R., Duff, S.J.B. and Kosaric, N. 1981. Enhanced production of surfactin from Bacillus subtilis by continuous product removal and metal cation additions. Appl. Environ. Microbiol. 42: 408–412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Sheppard, J.D. and Mulligan, C.N. 1987. The production of surfactin by Bacillus subtilis grown on peat hydrolysate. Appl. Microbiol. Biotechnol. 27: 110–116.

    Article  CAS  Google Scholar 

  31. Sandrin, C., Peypoux, F. and Michel, G. 1990. Coproduction of surfactin and iturin A, lipopeptides with surfactant and antifungal properties, by Bacillus subtilis . Biotechnol. Appl. Biochem. 12: 370–375.

    CAS  PubMed  Google Scholar 

  32. Persson, A., Österberg, E. and Dostalek, M. 1988. Biosurfactant production by Pseudomonas fluorescens 378: growth and product characteristics. Appl. Microbiol. Biotechnol. 29: 1–4.

    Article  CAS  Google Scholar 

  33. Pareilleux, A. 1979. Hydrocarbon assimilation by Candida lipolytica: Formation of a biosurfactant; effects on respiratory activity and growth. Eur. J. Appl. Microbiol. Biotechnol. 8: 91–101.

    Article  CAS  Google Scholar 

  34. Zajic, J.E., Guignard, H. and Gerson, D.F. 1977. Properties and bio'degradation of a bioemulsifier from Corynebacterium hydrocarboclastus . Biotechnol. Bioeng. 19: 1303–1320.

    Article  CAS  PubMed  Google Scholar 

  35. Jones, G.E. and Starkey, R.L. 1961. Surface-active substances produced by Thiobacillus thiooxidans J. Bacteriol. 82: 788–789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Beebe, J.L. and Umbreit, W.W. 1971. Extracellular lipid of Thiobacillus thiooxidans J. Bacteriol. 108: 612–614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cooper, D.G., Zajic, J.E. and Gerson, D.F. 1979. Production of surface-active lipids by Corynebacterium lepus . Appl. Environ. Microbiol. 37: 4–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gerson, D.F. and Zajic, J.E. 1978. Surfactant production from hydrocarbons by Corynebacterium lepus, sp. nov. and Pseudomonas asphaltmicus, sp. nov. Dev. Ind. Microbiol. 19: 577–599.

    Google Scholar 

  39. MacDonald, C.R., Cooper, D.G. and Zajic, J.E. 1981. Surface-active lipids from Nocardia erythropolis grown on hydrocarbons. Appl. Environ. Microbiol. 41: 117–123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hisatsuka, K., Nakahara, T., Sano, N. and Yamada, K. 1971. Formation of rhamnolipid by Pseudomonas aeruginosa and its function in hydrocarbon fermentation Agr. Biol. Chem. 33: 686–692.

    Article  Google Scholar 

  41. Ristau, E. and Wagner, F. 1983. Formation of novel anionic trehalose-tetraesters from Rhodococcus erythropolis under growth limiting conditions. Biotechnol. Lett. 5: 95–100.

    Article  CAS  Google Scholar 

  42. Itoh, A., Honda, H., Tomita, F. and Suzuki, T. 1971. Rhamnolipids produced by Pseudomonas aeruginosa grown on n-paraffin J. Antibiotics 24: 855–859.

    Article  CAS  Google Scholar 

  43. Kakinuma, A., Ouchida, A., Shima, T., Sugino, H., Isono, M., Tamura, G. and Arima, K. 1969. Confirmation of the structure of surfactin by mass spectrometry Agr. Biol. Chem. 33: 1669–1671.

    Article  CAS  Google Scholar 

  44. Kretschmer, A., Bock, H. and Wagner, F. 1982. Chemical and physical characterization of interfacial-active lipids from Rhodococcus erythropolis grown on n-alkanes Appl. Environ. Microbiol. 44: 864–870.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Akit, J., Cooper, D.G., Manninen, K.I. and Zajic, J.E. 1981. Investigation of potential biosurfactant production among phytopathogenic Corynebacteria and related soil microbes Current Microbiol. 6: 145–150.

    Article  CAS  Google Scholar 

  46. Goursad, J.-C. 1989. Production of a biosurfactant by Bacillus lickeniformis JF-2. Thesis, The University of Texas, Austin, TX.

    Google Scholar 

  47. Syldatk, C. and Wagner, F. 1987. Production of Biosurfactants. In: Biosurfactants and Biotechnology. Kosaric, N., Cairns, W. L., and Gary, N. C. C. (Eds.). Marcel Decker, Inc., NY.

    Google Scholar 

  48. Greiner, M. and Winkelman, G. 1987. Fermentation and isolation of herbicolin A, a peptide produced by Erwinia herbicola strain A111. Appl. Microbiol. Biotechnol. 34: 565–569.

    Article  Google Scholar 

  49. Kretschmer, A. and Wagner, F. 1983. Characterization of biosynthetic intermediates of trehalose dicorynomycolates from Rhodococcus erythropolis grown on n-alkanes. Biochim. Biophys. Acta. 753: 306–313.

    Article  CAS  Google Scholar 

  50. Suzuki, T., Tanaka, H. and Itoh, S. 1974. Sucrose lipids of Arthrobacteria, Corynebacteriaand Nocardiagrown on sucrose Agr. Biol. Chem. 38: 557–563.

    Article  CAS  Google Scholar 

  51. Itoh, S. and Suzuki, T. 1974. Fructose-lipids of Arthrobacter, Corynebacteria, Nocardia and Mycobacteria grown on fructose. Agr. Biol. Chem. 38: 1443–1449.

    Article  CAS  Google Scholar 

  52. Boulton, C.A. and Ratledge, C. 1987. Biosynthesis of lipid precursors to surfactant production. In: Biosurfactants and Biotechnology. Kosaric, N., Cairns, W. L., and Gary, N. C. C. (Eds.). Marcel Decker Inc., NY.

    Google Scholar 

  53. Vater, J., 1984. Lipopeptides, an interesting class of microbial secondary metabolites. Progr. Colloid Polymer Sci. 72: 12–18.

    Article  Google Scholar 

  54. Kleinkauf, H. and von Döhren, H. Biosynthesis of peptide antibiotics. Ann. Rev. Microbiol. 41: 259–289.

    Article  CAS  PubMed  Google Scholar 

  55. Nakano, M.M. and Zuber, P. 1990. Molecular biology of antibiotic production in Bacillus CRC Critical Reviews in Biotechnol. 10: 223–240.

    Google Scholar 

  56. Nakano, M.M., Corbell, N. and Zuber, P. 1991. Isolation and characterization of sfp: a gene required for the production of the lipopeptide biosurfactant, surfactin, in Bacillus subtilis . Mol. Gen. Genet. In press.

  57. Kluge, B., Vater, J., Salnikow, J. and Eckart, K. 1988. Studies on the biosynthesis of surfactin, a lipopeptide antibiotic from Bacillus subtilis ATCC 21332. FEES Lett. 231: 107–110.

    Article  CAS  Google Scholar 

  58. Ullrich, C., Kluge, B., Palacz, Z. and Vater, J. 1991. Cell-free biosynthesis of surfactin, a cyclic lipopeptide produced by Bacillus subtilis . Biochemistry 30: 6503–6508.

    Article  CAS  PubMed  Google Scholar 

  59. Leahy, J.G. and Colwell, R.R. 1990. Microbial degradation of hydrocarbons in the environment Microbiol. Rev. 54: 305–315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Broderick, L.S. and Cooney, J.J. 1982. Emulsification of hydrocarbons by bacteria from freshwater ecosystems. Dev. Ind. Microbiol. 23: 425–434.

    Google Scholar 

  61. Oberbremer, A., Müller-Hurtig, R. and Wagner, F. 1990. Effect of the addition of microbial surfactants on hydrocarbon degradation in a soil population in a stirred reactor Appl. Microbiol. Biotechnol. 32: 485–489.

    Article  CAS  PubMed  Google Scholar 

  62. Harvey, S., Elashvili, I., Valdes, J.J., Kamely, D. and Chakrabarty, A.M. 1990. Enhanced removal of Exxon Valdez spilled oil from Alaskan gravel by a microbial surfactant Bio/Technol. 8: 228–230.

    CAS  Google Scholar 

  63. Kaeppeli, O. and Fiechter, H. 1976. The mode of interaction between the substrate and cell surface of the hydrocarbon utilizing yeast Candida tropicalis . Biotechnol. Bioeng. 18: 967–974.

    Article  CAS  PubMed  Google Scholar 

  64. Kaeppeli, O. and Fiechter, A. 1977. Component from the cell surface of the hydrocarbon-utilization yeast Candida tropicalis with possible relation to hydrocarbon transport. J. Bacteriol. 131: 917–921.

    Article  CAS  Google Scholar 

  65. Bar-Ness, R., Avrahamy, N., Matsuyama, T. and Rosenberg, M. 1988. Increased cell surface hydrophobicity of a Serratia marcescens NS 38 mutant lacking wetting activity J. Bacteriol. 170: 4361–4364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kochi, M., Weiss, D.W., Pugh, L.H. and Groupe, V.,1951. Viscosin, a new antibiotic Bacteriological Proc. 51: 29–30.

    Google Scholar 

  67. Bernheimer, A.W. and Avigad, L.S. 1970. Nature and properties of a cytolytic agent produced by Bacillus subtilis . J. Gen. Microbiol. 61: 361–369.

    Article  CAS  PubMed  Google Scholar 

  68. Kurioka, S. and Liu, P.V. 1967. Effect of the hemolysin of Pseudomonas aeruginosa on phophatides and on phospholipase c activity. J. Bacteriol. 93: 670–674.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Bailey, J.E. 1991. Towards a science of metabolic engineering Science 252: 1668–1675.

    Article  CAS  PubMed  Google Scholar 

  70. Stephanopoulos, G. and Valine, J.J. 1991. Network rigidity and metabolic engineering in metabolite overproduction. Science 252: 1675–1681.

    Article  CAS  PubMed  Google Scholar 

  71. Koch, A.K., Reiser, J., Käppeli, O. and Fiechter, A. 1988. Genetic construction of lactose-utilizing strains of Pseudomonas aeruginosa and their application in biosurfactant production Bio/Technology 6: 1335–1339.

    CAS  Google Scholar 

  72. Matsuyama, T., Sogawa, M. and Yano, I. 1991. Direct colony thin-layer chromatography and rapid characterization of Serratia marcescens mutants defective in production of wetting agents. Appl. Environ. Microbiol. 53: 1186–1188.

    Article  Google Scholar 

  73. Koch, A.K., Käppeli, O., Fiechter, A. and Reiser, K. 1991. Hydrocarbon assimilation and biosurfactant production in Pseudomonas aeruginosa mutants. J. Bacteriol. 173: 4212–4219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Mulligan, C.N., Cooper, D.G. and Neufeld, R.J. 1984. Selection of microbes producing biosurfactants in media without hydrocarbons. J. Ferment. Technol. 62: 311–314.

    CAS  Google Scholar 

  75. Mulligan, C.N., Chow, T.Y.K. and Gibbs, B. 1989. Enhanced biosurfactant production by a mutant Bacillus subtilis strain Appl. Microbiol. Biotechnol. 31: 486–489.

    Article  CAS  Google Scholar 

  76. Nakano, M.M. and Zuber, P. 1988. Identification of a genetic locus required for biosynthesis of the lipopeptide antibiotic surfactin in Bacillus subtilis . J. Bacteriol. 170: 5662–5668.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Nakano, M.M., Magnuson, R., Myers, A., Curry, J., Grossman, A.D. and Zuber, P. 1991. srfA is an operon required for surfactin production, competence development and efficient sporulation in Bacillus subtilis. J. Bacteriol. 173: 1770–1778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Crossman, A. 1991. Integration of developmental signals and the initiation of sporulation in B subtilis. Cell. 65: 5–8.

    Article  Google Scholar 

  79. Nakano, M.M. and Zuber, P. 1991. Transcription initiation region of the srfA operon, which is controlled by the comP-comA signal transduction system in Bacillus subtilis . J. Bacteriol. In press.

  80. Guerra-Santos, L., Käppeli, O. and Fiechter, A. 1984. Pseudomonas aeruginosa biosurfactant production in continuous culture with glucose as carbon source. Appl. Environ. Microbiol. 48: 301–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Suzuki, T., Tanaka, K. and Kinoshita, S. 1969. The extracellular accumulation of trehalose and glucose by bacteria grown on n-alkanes Agr. Biol. Chem. 33: 190–195.

    Article  CAS  Google Scholar 

  82. Rubinowitz, C., Gutnick, D.L. and Rosenberg, E. 1982. Emulsan production by Acinetobacter calcoaceticus in the presence of chloram-phenicol J. Bacteriol. 152: 126–132.

    Article  Google Scholar 

  83. Rosenberg, E., Zuckerberg, A., Rubinovitz, C. and Gutnick, D.L. 1979. Emulsifier of ArthrobacterRAG-1: Isolation and emulsifying properties Appl. Environm. Microbiol. 37: 402–408.

    Article  CAS  Google Scholar 

  84. Iguchi, T., Takeda, I. and Ohsawa, H. 1969. Emulsifying factor of hydrocarbon produced by a hydrocarbon-assimilating yeast Agr. Biol. Chem. 33: 1657–1658.

    Article  CAS  Google Scholar 

  85. Mulligan, C.N. and Gibbs, B.F. 1990. Recovery of biosurfactants by ultrafiltration. J. Chem. Tech. Biotechnol. 47: 23–29.

    Article  CAS  Google Scholar 

  86. Kachholtz, T. and Schlingmann, M. 1987. Possible food and agricultural applications of microbial surfactants: An assessment. In: Biosurfactants and Biotechnology. Kosaric, N., Cairns, W. L., and Gary, N. C. C. (Eds.). Marcel Decker, Inc., NY.

  87. Horowitz, S. and Currie, J.K. 1990. Novel dispersants of silicon and aluminum nitride J. Dispersion Sci. Technol. 11: 637–659.

    Article  CAS  Google Scholar 

  88. Brown, M.J., Robinson, J.P. and Springham, D.G. 1986. Microbial enhanced oil recovery: progress and prospects CRC Crit. Rev. in Biotechnol. 3: 159–197.

    Article  CAS  Google Scholar 

  89. Sarkar, A.K., Goursaud, J.-C., Sharma, M.M. and Georgiou, G. 1990. A critical evaluation of MEOR processes In situ 13: 207–238.

    Google Scholar 

  90. Oberbremer, A., Muller-Hurtig, R. and Wagner, F. 1990. Effect of the addition of microbial surfactants on hydrocarbon degradation in a soil population in a stirred reactor. Appl. Microbiol. Biotechnol. 32: 485–489.

    Article  CAS  PubMed  Google Scholar 

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  1. George Georgiou: Corresponding author.

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  1. Department of Chemical Engineering, University of Texas, Austin, TX, 78712

    George Georgiou & Sung-Chyr Lin

  2. Department of Petroleum Engineering, University of Texas, Austin, TX, 78712

    Mukul M. Sharma

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Georgiou, G., Lin, SC. & Sharma, M. Surface–Active Compounds from Microorganisms. Nat Biotechnol 10, 60–65 (1992). https://doi.org/10.1038/nbt0192-60

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