New Polycyclic Tetramate Macrolactam from Streptomyces sp. S001

Montamide A (1), a new polycyclic tetramate macrolactam (PoTeM) with a 5/5/6 tricyclic system was isolated from recombinant strain S001-PoTeMS023, which is derived from Streptomyces sp. S001 by introducing a new PoTeM biosynthetic gene cluster cft(S023). The chemical structure of 1 was elucidated by different spectroscopic techniques including FIRMS, 1D and 2D-NMR and ECD spectroscopies. The antibacterial and antifungal activities of compound 1 were carried out by filter paper disc diffusion assay. The results showed that compound 1 has no effect on tested strains at 40 mu g/disc. The cytotoxicity of compound 1 was evaluated by methyl thiazolyl tetrazolium (MTT) assay using doxonthicin as a positive control. Compound 1 showed weak antiproliferative activity against human lung carcinoma cell line A549 (IC50 similar to 22.6 mu mol/L), and the substitution at C16 was critical for the cytotoxicity of compound 1. In addition, the biosynthetic gene cluster of compound 1 was identified and the biosynthetic pathway of compound 1 was proposed.