Heronamides with unreported skeletons from deep-sea Streptomyces: discovery and biosynthesis

Abstract

Heronamides M–Q (1–5), five new polyketide macrolactams, among which 1 and 2 feature unreported 6/6/6/5/5-pentacyclic and 6/9/6/5-tetracyclic skeletons, respectively, along with four known heronamides (6–9), were isolated from the deep-sea-derived Streptomyces sp. OUCT16-38. The planar structures and stereochemistry of 1–5 were established based on extensive MS and NMR spectroscopic analyses together with ECD calculations. Furthermore, a plausible biosynthetic pathway of 1–9 was proposed. Upon antibacterial activity evaluation, 8 and 9 showed considerable growth inhibition against the multi-drug resistant pathogens Enterococcus faecium CCARM 5203 and Enterococcus faecalis CCARM 5172 with an MIC value of 3.1 μg mL⁻¹, and exhibited low toxicity (IC₅₀ values of 18.7 and 39.4 μM) towards human hepatocytes.