文章基本信息

标题：Aquastatin A, a New Inhibitor of Enoyl-Acyl Carrier Protein Reductase from Sporothrix sp. FN611
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作者：Yun-Ju Kwon ; Yi Fang ; Guang-Hua Xu 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2009
卷号：32
期号：12
页码：2061-2064
DOI：10.1248/bpb.32.2061
出版社：The Pharmaceutical Society of Japan
摘要：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 IC₅₀ of 3.2 μ M . It also prevented the growth of S. aureus and methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration of 16—32μg/ml. Aquastatin A also exerted an inhibitory effect against the FabK isoform, an enoyl-ACP reductase of Streptococcus pneumoniae , with an IC₅₀ of 9.2 μ M . 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.
关键词：aquastatin A;enoyl-acyl carrier protein reductase;Staphylococcus aureus;FabI;fungal metabolite;inhibitor