title: Panosialins, inhibitors of enoyl-ACP reductase from Streptomyces sp. AN1761.
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 microM than M. tuberculosis InhA with IC50 of 9-12 microM. 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.
authors: Environmental Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
authors: Yun Ju
authors: YJ
authors: Kwon
authors: Mi-Jin
authors: MJ
authors: Sohn
authors: Taegwon
authors: T
authors: Oh
authors: Sang-Nae
authors: SN
authors: Cho
authors: Chang-Jin
authors: CJ
authors: Kim
authors: Won-Gon
authors: WG
authors: Kim
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D001555:Benzene Derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D001555:Benzene Derivatives; D004791:Enzyme Inhibitors; D005227:Fatty Acids; C003039:panosialin; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)