Isolation of a novel cyclic hexadepsipeptide pipalamycin from Streptomyces as an apoptosis-inducing agent.

The novel cyclic hexadepsipeptide named pipalamycin was isolated from a culture filtrate of Streptomyces sp. ML297-90F8 as an apoptosis-inducing agent. The antibiotic was found to be consisting of each one mole of alanine, N-hydroxyalanine, glycine, N-acylated 3-hydroxyleucine, and two moles of piperazic acid. Pipalamycin induced apoptosis in apoptosis-resistant human pancreatic adenocarcinoma AsPC-1 cells at 0.3 microg/ml in 24 to approximately 48 hours. It also showed antibacterial activity on Gram-positive bacteria such as Staphylococcus aureus and Micrococcus luteus. Fermentation, isolation, structural elucidation and the biological activities of pipalamycin are described.