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Analytical and Bioanalytical Chemistry

, Volume 388, Issue 5–6, pp 1117–1125 | Cite as

Biosensor-guided screening for macrolides

  • V. Möhrle
  • M. Stadler
  • G. Eberz
Original Paper

Abstract

Macrolides are complex polyketides of microbial origin that possess an extraordinary variety of pharmacological properties, paired with an impressive structural diversity. Bioassays for specific detection of such compounds will be of advantage for a class-specific drug screening. The current paper describes a cell-based microbial biosensor, assigning a luminescence response to natural or chemically modified macrolides, independent from their biological activity. This biosensor is based on the coupling of the structural luciferase genes of Vibrio fischeri to the regulatory control mechanism of a bacterial erythromycin resistance operon. The bioassays is easy to handle and can be applied to various screening formats. The feasibility of the test system for natural products screening is exemplified by the isolation and characterization of picromycin from a Streptomyces species.

Biosensor-guided screening for macrolides is based on macrolide-promoted expression of lux genes and induction of luminescence (independent of macrolide antibiotic activity)

Keywords

Bioluminescence Biosensor Macrolide Natural product Reporter gene 

Notes

Acknowledgements

We thank Anke Mayer-Bartschmid from Bayer HealthCare AG for the cultivation and lyophilization of bacterial strains.

References

  1. 1.
    Daunert S, Barrett G, Feliciano JS, Shetty RS, Shrestha S, Smith-Spencer W (2000) Chem Rev 100:2705–2738CrossRefGoogle Scholar
  2. 2.
    Kurittu J, Karp M, Korpela M (2000) Luminescence 15:291–297CrossRefGoogle Scholar
  3. 3.
    Peitzsch N, Eberz G, Nies DN (1998) Appl Environ Microbiol 64:453–458Google Scholar
  4. 4.
    Ludwig C, Ecker S, Schwindel K, Rast HG, Stetter KO, Eberz G (1999) Arch Microbiol 172:45–50CrossRefGoogle Scholar
  5. 5.
    Weber W, Fux C, Daoud-El Baba M, Keller B, Weber CC, Kramer BP, Heinzen C, Aubel D, Bailey JE, Fussenegger M (2002) Nature Biotech 20:901–907CrossRefGoogle Scholar
  6. 6.
    Weber CC, Link N, Fux C, Zisch AH, Weber W, Fussenegger M (2004) Biotech Bioeng 89:9–17CrossRefGoogle Scholar
  7. 7.
    Kawamura O, Sekuguchi T, Itoh Z, Omura S (1993) Dig Dis Sci 38:1026–1031CrossRefGoogle Scholar
  8. 8.
    Verhagen MA, Samsom M, Maes B, Geypens BJ, Ghoos YF, Smout AJPM (1997) Aliment Pharmacol Ther 11:1077–1088CrossRefGoogle Scholar
  9. 9.
    Wang L, Kitaichi K, Hui CS, Takagi K, Sakai M, Yokogawa K, Miyamoto K, Hasegawa T (2000) Clin Exp Pharmacol Physiol 27:587–593CrossRefGoogle Scholar
  10. 10.
    Hamada K, Mikasa K, Yunou Y, Kurioka T, Majima T, Narita N, Kita E (2000) Chemother 46:49–61CrossRefGoogle Scholar
  11. 11.
    Omura S, Tanaka H (1984) In: Omura S (ed) Macrolide antibiotics: chemistry, biology, and practice. Academic Press, Orlando, USA, pp 3–35Google Scholar
  12. 12.
    Bryskier A (2001) Exp Opin Invest Drugs 10:239–267CrossRefGoogle Scholar
  13. 13.
    Bryskier A (1997) Exp Opin Invest Drugs 6:1697–1709CrossRefGoogle Scholar
  14. 14.
    von Nussbaum F, Brands M, Hinzen B, Weigand S, Häbich D (2006) Angew Chem Int Ed 45:5072–5129CrossRefGoogle Scholar
  15. 15.
    Noguchi N, Takada K, Katayama J, Emura A, Sasatsu M (2000) J Bacteriol 182:5052–5058CrossRefGoogle Scholar
  16. 16.
    Eberz G, Rast HG, Burger K, Kreiss W, Weisemann C (1996) Chromatographia 43:5–9CrossRefGoogle Scholar
  17. 17.
    Herrero M, de Lorenzo V, Timmis KN (1990) J Bacteriol 172:6557–6567Google Scholar
  18. 18.
    Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar
  19. 19.
    Hopwood DA, Bibb MJ, Chater CP, Kieser T, Bruton CJ, Kieser HM, Lydiate DJ, Smith CP, Ward JM, Schrempf WH (1985) Genetic manipulation of Streptomyces, a laboratory manual. John Innes Institution, Norwich UKGoogle Scholar
  20. 20.
    Chang ACY, Cohen SN (1978) J Bacteriol 1978:1141–1156Google Scholar
  21. 21.
    Rogowsky PM, Close TJ, Chimera JA, Shaw JJ, Kado CI (1987) J Bacteriol 169:5101–5112Google Scholar
  22. 22.
    Alexeyev MF, Shokolenko IN (1995) Gene 160:59–62CrossRefGoogle Scholar
  23. 23.
    Dunn JJ, Studier FW (1983) J Mol Biol 166:477–535CrossRefGoogle Scholar
  24. 24.
    Gerten G (1993) Oxoid Handbuch, 5. Aktualisierte Deutsche Auflage, Verlag R. Meyer, DüsseldorfGoogle Scholar
  25. 25.
    Hellwig V, Ju Y-M, Rogers JD, Fournier J, Stadler M (2005) Mycol Progr 4(1):39–54CrossRefGoogle Scholar
  26. 26.
    Omura S, Takeshima H, Nakagawa A, Miyazawa J (1976) J Anibiot 29:317–318Google Scholar
  27. 27.
    Vuorio R, Vaara M (1992) Antimicrob Agents Chemother 36:826–829Google Scholar
  28. 28.
    Brodersen R, Bunch-Christensen K, Tybring L (1953) Acta Pharmacol Toxicol 9:255–258CrossRefGoogle Scholar
  29. 29.
    DE 2001-10138766, WO2003014386Google Scholar
  30. 30.
    Xue Q, Ashley G, Hutchinson R, Santi DV (1999) Proc Natl Acad Sci 96:11740–11745CrossRefGoogle Scholar
  31. 31.
    Pfeifer BA, Admiraal SJ, Gramajo H, Cane DE (2001) Science 291:1790–1792CrossRefGoogle Scholar
  32. 32.
    Coco WM, Levinson WF, Christ MJ, Hektor HJ, Darzins A, Pienkos PT, Squires CH, Monticello DJ (2001) DNA Nature Biotech 19:354–359CrossRefGoogle Scholar
  33. 33.
    Zhao HM, Giver L, Shao ZX, Affholter JA, Arnold FH (1998) Nature Biotech 16:258–261CrossRefGoogle Scholar
  34. 34.
    Stemmer WPC (1994) Proc Nat Acad Sci 91:10747–10751CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Bayer Technology Services GmbHLeverkusenGermany
  2. 2.InterMed Discovery GmbHDortmundGermany
  3. 3.Corporate CenterBayer AGLeverkusenGermany

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