Leptomycin B (LMB), a secondary metabolite produced by Streptomyces sp
, strain ATS 1287, with known antifungal and antitumor effects, inhibi
ts the nucleo-cytoplasmic translocation of the human immunodeficiency
virus type 1 regulatory protein Rev and exhibits significant antiproli
ferative activity. Since LMB itself turned out to be distinctly cytoto
xic, a bioconversion screening with a selected set of 29 bacterial and
72 fungal strains was performed in order to obtain metabolites of LMB
with reduced antiproliferative effects, Several derivatives of LMB, m
ore polar than the parent compound and produced in yields of >5%, were
detected, Liquid chromatography-mass spectroscopy analysis indicated
the type of bioconversion, Fermentations (1-liter scale) of those stra
ins with high rates of transformation were suitable for isolation and
characterization of the most prominent metabolites, Thus, bioconversio
n of LMB with Aspergillus flavus ATCC 9170 and Emericella unguis ATCC
13431 served for isolation of the novel derivatives 26-hydroxy-LMB (30
% was the concentration metabolite [with respect to LMB] used for bioc
onversion) and LMB-24-glutaminamide (90%), respectively, Streptomyces
rimosus ATCC 28893 converted LMB into 4,11-dihydroxy-LMB (13%) and 2,3
-dihydro-LMB (55%). Although the antiproliferative effects of the LMB
metabolites could be reduced through microbial conversion, none of the
se metabolites inhibited the nuclear export of Rev better than LMB its
elf.