Panosialins, inhibitors of Enoyl-ACP reductase from Streptomyces sp. AN1761 = Streptomyces sp. AN1761로부터 분리한 에노일 리덕타제 저해제 파노시알린

Abstract

In the continued search for inhibitors of enoyl-acyl carrier protein (ACP) reductase, we found that four acylbenzenediol sulfate metabolites from Streptomyces sp. AN1761 potently inhibited bacterial enoyl-ACP reductases of Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis. Their structures were identified as panosialins A, B, wA, and wB by MS and NMR data. They showed stronger inhibition against S. aureus FabI and S. pneumoniae FabK with IC50 of 3-5 μM than M. tuberculosis InhA with IC50 of 9-12 μM. They also exhibited a stronger antibacterial spectrum on S. aureus and S. pneumoniae than M. tuberculosis. In addition, the higher inhibitory activity of panosialin wB than panosialin B on fatty acid biosynthesis was consistent with that on bacterial growth, suggesting that they could exert their antibacterial activity by inhibiting fatty acid synthesis.