Abstract
Streptomyces sp. K97-0239, a soil isolate, was found to produce inhibitors of lipid droplet formation in mouse peritoneal macrophages. Two compounds, K97-0239A and B, were isolated from the culture broth of the producing strain, and their structures were elucidated by spectroscopic analyses including various NMR experiments. They were cyclic lipopeptides comprising 2, 3-diaminopropionic acid, 4-(aminomethyl)-2, 2-dimethyl-5-oxo-1-imidazolidineacetic acid and phenylalanine/leucine as ring units, and 3-(13-hydroxytetradeca-2, 4-dienoylamino)-acrylic acid as lipophilic side chains. They caused a dose-dependent reduction in the number and size of cytosolic lipid droplets in macrophages at least up to 15μM without any cytotoxic effect on macrophages. [14C] Cholesteryl ester synthesis from [14C] oleic acid by macrophages was inhibited by K97-0239s with IC50 values of 1.5-1.7μM.
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