Biosynthesis of amphotericin B

(Note: The full text of this document is currently only available in the PDF Version )

Carmel M. McNamara, Stephen Box, James M. Crawforth, Benjamin S. Hickman, Timothy J. Norwood and Bernard J. Rawlings


Abstract

The high level incorporation of isotopically labelled sodium acetate and sodium propionate into amphotericin B is reported. Double quantum filtered heteronuclear single quantum coherence NMR (DQF-HSQC) is employed to demonstrate coupling between labelled carbons on intact acetate units after biosynthesis. Electrospray mass spectroscopy demonstrates the high level incorporation of label is present in only half the molecules, the other half remaining unlabelled.


References

  1. T. H. Sternberg, E. T. Wright and M. Oura, Antibiot. Annu., 1956, 566 Search PubMed; B. A. Steinberg, W. P. Jambar and L. O. Suydam, Antibiot. Annu., 1956, 574 Search PubMed; W. Gold, H. A. Stout, J. F. Pagano and R. Donovick, Antibiot. Annu., 1956, 579 Search PubMed; J. Vandeputte, J. L. Wachtel and E. T. Stiller, Antibiot. Annu., 1956, 587 Search PubMed.
  2. W. Mechlinski, C. P. Schaffner, P. Ganis and G. Avitabile, Tetrahedron Lett., 1970, 3873 CrossRef CAS; P. Ganis, G. Avitabile, W. Mechlinski and C. P. Schaffner, J. Am. Chem. Soc., 1971, 93, 4560 CrossRef CAS.
  3. K. C. Nicolaou, T. K. Chakraborty, Y. Ogawa, R. A. Daines, N. S. Simpkins and G. T. Furst, J. Am. Chem. Soc., 1988, 110, 4660 CrossRef CAS; K. C. Nicolaou, R. A. Daines, J. Uenishi, W. S. Li, D. P. Papahatjis and T. K. Chakraborty, J. Am. Chem. Soc., 1988, 110, 4672 CrossRef CAS.
  4. K. C. Nicolaou, R. A. Daines, T. K. Chakraborty and Y. Ogawa, J. Am. Chem. Soc., 1988, 110, 4685 CrossRef CAS.
  5. K. C. Nicolaou, R. A. Daines, Y. Ogawa and T. K. Chakraborty, J. Am. Chem. Soc., 1988, 110, 4696 CrossRef CAS.
  6. B. DeKruijff and R. A. Demel, Biochim. Biophys. Acta, 1974, 339, 57 CAS; V. E. Khutorsky, Biochim. Biophys. Acta, 1992, 1108, 123 CAS; D. E. Mickus, D. G. Levitt and S. D. Rychnovsky, J. Am. Chem. Soc., 1992, 114, 359 CrossRef CAS; P. R. James and B. J. Rawlings, Bioorg. Med. Chem. Lett., 1996, 6, 505 CrossRef CAS.
  7. C. P. Schaffner, Macrolide Antibiotics, Chemistry, Biology, and Practice, ed. S. Õmura, Academic Press, Orlando, 1984, p. 457 Search PubMed; N. H. Georgopapadakou and T. G. Walsh, Science, 1994, 264, 371 Search PubMed.
  8. J. Staunton, Angew. Chem., Int Ed. Engl., 1991, 30, 1302 CrossRef.
  9. P. H. Harrison, H. Noguchi and J. C. Vederas, J. Am. Chem. Soc., 1986, 108, 3833 CrossRef CAS.
  10. (a) H. A. B. Linke, W. Mechlinski and C. P. Schaffner, J. Antibiot., 1974, 27, 155 CAS; (b) D. Perlman and J. B. Semar, Biotechnol. Bioeng., 1965, 7, 133 CAS.
  11. M. J. Rees, E. A. Cutmore and M. S. Verrall, Separations for Biotechnology, ed. D. L. Pyler, The Royal Society of Chemistry, Cambridge, UK, 1994, 3rd edition, pp. 399–405 Search PubMed.
  12. N. Monji, D. P. Bonner, Y. Hashimoto and C. P. Schaffner, J. Antibiot., 1975, 28, 317 CAS; N. Monji, W. Mechlinski and C. P. Schaffner, J. Antibiot., 1976, 29, 438 CAS.
  13. A. Aszalos, A. Bax, N. Burlinson, P. Roller and C. McNeal, J. Antibiot., 1985, 38, 1699 CAS.
  14. H. Kessler, H. Oschkinat and C. Griesinger, J. Magn. Reson., 1986, 70, 106 CAS.
  15. D. O'Hagan, S. V. Rogers, K. A. Reynolds and G. R. Duffin, J. Chem. Soc., Chem. Commun., 1994, 1577 RSC.
Click here to see how this site uses Cookies. View our privacy policy here.