Phenylacetyl pepstatin inhibitors of aspartyl proteases from Streptomyces varsoviensis.

A new pepstatin with a phenylacetyl group, pepstatin Pa (1), and its methyl ester (2) were isolated from Streptomyces varsoviensis DSM 40346. Their structures were determined by high-resolution mass spectrometry and nuclear magnetic resonance techniques. The absolute configuration was determined using the Marfey's method. Both pentapeptide products are inhibitors of pepsin and cathepsin D. Interestingly, the bacterial genome contains no biosynthetic gene cluster for the new pepstatin, suggesting an extrachromosomal origin of the biosynthetic genes.