Discovery of a New Polycyclic Tetramate Macrolactam 3-Hydroxycombamide I

3-Hydroxycombamide I (2), a new polycyclic tetramate macrolactam (PoTeM) bearing a 5/5/6 cyclization pattern was isolated from the recombinant strain S001-cbm-OX4-ikaD, which is derived from Streptomyces sp. S001 by integration of the modified combamides biosynthetic gene cluster. The chemical structure of 2 was determined by analysis of 1D and 2D-NMR and HRMS data. The hydroxylation of compound 2 at C-3 was deduced to be catalyzed by a hydroxylase of Streptomyces sp. S001. The antibacterial and cytotoxic activity of compound 2 was evaluated by filter paper disc diffusion and methyl thiazolyl tetrazolium (MTT) assay, respectively. The effect of compound 2 on inhibition of the T3SS (type III secretion system) of Salmonella enterica serovar Typhimurium was also investigated. However, compound 2 was inactivity in all assays. The results indicated that the hydroxylation at C-3 may occurs after the oxidative modifictions of the polycyclic system in the biosynthesis of PoTeMs.

Automated summary

A new polycyclic tetramate macrolactam was isolated from a recombinant strain of Streptomyces. The chemical structure and biological activities of the compound were investigated, shedding light on the biosynthesis pathway of polycyclic tetramate macrolactams.