Aquastatin A, a New Inhibitor of Enoyl-Acyl Carrier Protein Reductase from Sporothrix sp. FN611
| Autor: | Yun-Ju Kwon, Won-Gon Kim, Guang-Hua Xu, Yi Fang |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
Gene isoform Staphylococcus aureus Enoyl-acyl carrier protein reductase Metabolite Pharmaceutical Science Microbial Sensitivity Tests Biology Reductase medicine.disease_cause Microbiology Inhibitory Concentration 50 Minimum inhibitory concentration chemistry.chemical_compound Streptococcus pneumoniae medicine Protein Isoforms IC50 Pharmacology Microbial Viability Sporothrix Galactosides General Medicine Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) Salicylates Anti-Bacterial Agents Biochemistry chemistry |
| Zdroj: | Biological and Pharmaceutical Bulletin. 32:2061-2064 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.32.2061 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|