Aquastatin A, a new inhibitor of enoyl-acyl carrier protein reductase from Sporothrix sp. FN611.
Bacterial enoyl-acyl carrier protein (ACP) reductase has been confirmed as a novel target for antibacterial drug development. In this study, we determined that a fungal metabolite from Sporothrix sp. FN611 potently inhibited the enoyl-ACP reductase (FabI) of Staphylococcus aureus. Its structure identified the metabolite as aquastatin A by the MS and NMR data. Aquastatin A inhibited S. aureus FabI with an IC(50) of 3.2 microM. It also prevented the growth of S. aureus and methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration of 16-32 microg/ml. Aquastatin A also exerted an inhibitory effect against the FabK isoform, an enoyl-ACP reductase of Streptococcus pneumoniae, with an IC(50) of 9.2 microM. The degalactosylation of aquastatin A did not affect the FabI and FabK-inhibitory or antibacterial activities, thereby suggesting that the sugar moiety within its molecular structure was not involved in these activities. The inhibitory effects of aquastatin A and its degalactosylated derivative on enoyl-ACP reductases and bacterial viability are reported for the first time in this study; these effects point to the potential that aquastatin A may be developed into a new broad-spectrum antibacterial and anti-MRSA agent.
Kwon
Yun-Ju
YJ
Korea Research Institute of Bioscience and Biotechnology, Yusong, Daejeon 305-806, Korea.
Fang
Yi
Y
Xu
Guang-Hua
GH
Kim
Won-Gon
WG
D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors*; D005697:Galactosides / Q000302:isolation & purification / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D020033:Protein Isoforms; D012459:Salicylates / Q000302:isolation & purification / Q000494:pharmacology*; D013175:Sporothrix / Q000737:chemistry* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development
D000900:Anti-Bacterial Agents; D005697:Galactosides; D020033:Protein Isoforms; D012459:Salicylates; C085031:aquastatin A; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)