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Biosensor-guided screening for macrolides

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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)

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References

  1. Daunert S, Barrett G, Feliciano JS, Shetty RS, Shrestha S, Smith-Spencer W (2000) Chem Rev 100:2705–2738

    Article  CAS  Google Scholar 

  2. Kurittu J, Karp M, Korpela M (2000) Luminescence 15:291–297

    Article  CAS  Google Scholar 

  3. Peitzsch N, Eberz G, Nies DN (1998) Appl Environ Microbiol 64:453–458

    CAS  Google Scholar 

  4. Ludwig C, Ecker S, Schwindel K, Rast HG, Stetter KO, Eberz G (1999) Arch Microbiol 172:45–50

    Article  CAS  Google Scholar 

  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 20:901–907

    Article  CAS  Google Scholar 

  6. Weber CC, Link N, Fux C, Zisch AH, Weber W, Fussenegger M (2004) Biotech Bioeng 89:9–17

    Article  CAS  Google Scholar 

  7. Kawamura O, Sekuguchi T, Itoh Z, Omura S (1993) Dig Dis Sci 38:1026–1031

    Article  CAS  Google Scholar 

  8. Verhagen MA, Samsom M, Maes B, Geypens BJ, Ghoos YF, Smout AJPM (1997) Aliment Pharmacol Ther 11:1077–1088

    Article  CAS  Google Scholar 

  9. Wang L, Kitaichi K, Hui CS, Takagi K, Sakai M, Yokogawa K, Miyamoto K, Hasegawa T (2000) Clin Exp Pharmacol Physiol 27:587–593

    Article  CAS  Google Scholar 

  10. Hamada K, Mikasa K, Yunou Y, Kurioka T, Majima T, Narita N, Kita E (2000) Chemother 46:49–61

    Article  CAS  Google Scholar 

  11. Omura S, Tanaka H (1984) In: Omura S (ed) Macrolide antibiotics: chemistry, biology, and practice. Academic Press, Orlando, USA, pp 3–35

    Google Scholar 

  12. Bryskier A (2001) Exp Opin Invest Drugs 10:239–267

    Article  CAS  Google Scholar 

  13. Bryskier A (1997) Exp Opin Invest Drugs 6:1697–1709

    Article  CAS  Google Scholar 

  14. von Nussbaum F, Brands M, Hinzen B, Weigand S, Häbich D (2006) Angew Chem Int Ed 45:5072–5129

    Article  CAS  Google Scholar 

  15. Noguchi N, Takada K, Katayama J, Emura A, Sasatsu M (2000) J Bacteriol 182:5052–5058

    Article  CAS  Google Scholar 

  16. Eberz G, Rast HG, Burger K, Kreiss W, Weisemann C (1996) Chromatographia 43:5–9

    Article  CAS  Google Scholar 

  17. Herrero M, de Lorenzo V, Timmis KN (1990) J Bacteriol 172:6557–6567

    CAS  Google Scholar 

  18. Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor

    Google Scholar 

  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 UK

    Google Scholar 

  20. Chang ACY, Cohen SN (1978) J Bacteriol 1978:1141–1156

    Google Scholar 

  21. Rogowsky PM, Close TJ, Chimera JA, Shaw JJ, Kado CI (1987) J Bacteriol 169:5101–5112

    CAS  Google Scholar 

  22. Alexeyev MF, Shokolenko IN (1995) Gene 160:59–62

    Article  CAS  Google Scholar 

  23. Dunn JJ, Studier FW (1983) J Mol Biol 166:477–535

    Article  CAS  Google Scholar 

  24. Gerten G (1993) Oxoid Handbuch, 5. Aktualisierte Deutsche Auflage, Verlag R. Meyer, Düsseldorf

  25. Hellwig V, Ju Y-M, Rogers JD, Fournier J, Stadler M (2005) Mycol Progr 4(1):39–54

    Article  Google Scholar 

  26. Omura S, Takeshima H, Nakagawa A, Miyazawa J (1976) J Anibiot 29:317–318

    Google Scholar 

  27. Vuorio R, Vaara M (1992) Antimicrob Agents Chemother 36:826–829

    CAS  Google Scholar 

  28. Brodersen R, Bunch-Christensen K, Tybring L (1953) Acta Pharmacol Toxicol 9:255–258

    Article  CAS  Google Scholar 

  29. DE 2001-10138766, WO2003014386

  30. Xue Q, Ashley G, Hutchinson R, Santi DV (1999) Proc Natl Acad Sci 96:11740–11745

    Article  CAS  Google Scholar 

  31. Pfeifer BA, Admiraal SJ, Gramajo H, Cane DE (2001) Science 291:1790–1792

    Article  CAS  Google Scholar 

  32. Coco WM, Levinson WF, Christ MJ, Hektor HJ, Darzins A, Pienkos PT, Squires CH, Monticello DJ (2001) DNA Nature Biotech 19:354–359

    Article  CAS  Google Scholar 

  33. Zhao HM, Giver L, Shao ZX, Affholter JA, Arnold FH (1998) Nature Biotech 16:258–261

    Article  CAS  Google Scholar 

  34. Stemmer WPC (1994) Proc Nat Acad Sci 91:10747–10751

    Article  CAS  Google Scholar 

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Acknowledgements

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

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Authors and Affiliations

  1. Bayer Technology Services GmbH, 51368, Leverkusen, Germany

    V. Möhrle

  2. InterMed Discovery GmbH, Otto-Hahn-Str 15, 44227, Dortmund, Germany

    M. Stadler

  3. Corporate Center, Bayer AG, 51368, Leverkusen, Germany

    G. Eberz

Authors
  1. V. Möhrle
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  2. M. Stadler
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  3. G. Eberz
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Correspondence to G. Eberz.

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Möhrle, V., Stadler, M. & Eberz, G. Biosensor-guided screening for macrolides. Anal Bioanal Chem 388, 1117–1125 (2007). https://doi.org/10.1007/s00216-007-1300-5

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  • DOI: https://doi.org/10.1007/s00216-007-1300-5

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