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Related Experiment Videos

Microbial conversion products of leptomycin B

M Kuhnt1, F Bitsch, M Ponelle

  • 1Core Technology Area, Research, Novartis Pharma Inc., Basel, Switzerland.

Applied and Environmental Microbiology
|February 17, 1998
PubMed
Summary

Microbial bioconversion of Leptomycin B (LMB) yielded novel derivatives with reduced antiproliferative effects. However, these LMB metabolites did not inhibit HIV-1 Rev nuclear export as effectively as the parent compound.

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Area of Science:

  • Microbiology
  • Natural Products Chemistry
  • Virology

Background:

  • Leptomycin B (LMB) is a potent antifungal and antitumor agent.
  • LMB inhibits HIV-1 Rev protein nuclear export but is highly cytotoxic.
  • Bioconversion offers a strategy to reduce LMB's cytotoxicity while retaining biological activity.

Purpose of the Study:

  • To screen microbial strains for the bioconversion of Leptomycin B (LMB).
  • To obtain LMB derivatives with reduced antiproliferative effects.
  • To characterize novel LMB metabolites and evaluate their biological activity.

Main Methods:

  • Screening of 29 bacterial and 72 fungal strains for LMB bioconversion.
  • Liquid chromatography-mass spectroscopy (LC-MS) for metabolite identification.

Related Experiment Videos

  • Fermentation and isolation of prominent LMB derivatives.

    • Main Results:

    • Several more polar LMB derivatives were produced in yields greater than 5%.
    • Novel derivatives isolated include 26-hydroxy-LMB, LMB-24-glutaminamide, 4,11-dihydroxy-LMB, and 2,3-dihydro-LMB.
    • Microbial conversion reduced antiproliferative effects, but no derivative outperformed LMB in inhibiting Rev nuclear export.

    Conclusions:

    • Microbial bioconversion is effective in generating LMB derivatives with modified properties.
    • The identified LMB metabolites show reduced cytotoxicity.
    • None of the novel derivatives matched the efficacy of Leptomycin B in inhibiting HIV-1 Rev nuclear export.