Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
J Microbiol Biotechnol. 2010 May;20(5):875-80. doi: 10.4014/jmb.1001.01004.
Bacterial enoyl-ACP reductase (FabI) has been demonstrated to be a novel antibacterial target. In the course of our screening for FabI inhibitors we isolated two methyl-branched fatty acids from Streptomyces sp. A251. They were identified as 14-methyl-9(Z)-pentadecenoic acid and 15-methyl-9(Z)-hexadecenoic acid by MS and NMR spectral data. These compounds inhibited Staphylococcus aureus FabI with IC50 of 16.0 and 16.3mu M, respectively, while didn't affect FabK, an enoyl-ACP reductase of Streptococcus pneumonia, at 100muM. Consistent with their selective inhibition for FabI, they blocked intracellular fatty acid synthesis as well as the growth of S. aureus, while didn't inhibit the growth of S. pneumonia. Additionally, these compounds showed reduced antibacterial activity against fabI-overexpressing S. aureus compared to the wild-type strain. These results demonstrate that the methyl-branched fatty acids showed antibacterial activity by inhibiting FabI in vivo.
细菌烯酰-ACP 还原酶 (FabI) 已被证实为一种新型的抗菌靶标。在我们筛选 FabI 抑制剂的过程中，从链霉菌 A251 中分离出两种支链脂肪酸。通过 MS 和 NMR 谱数据将它们鉴定为 14-甲基-9(Z)-十五碳烯酸和 15-甲基-9(Z)-十六碳烯酸。这些化合物对金黄色葡萄球菌 FabI 的抑制 IC50 分别为 16.0 和 16.3μM，而在 100μM 时对肺炎链球菌的烯酰-ACP 还原酶 FabK 没有影响。与它们对 FabI 的选择性抑制一致，它们阻断了细胞内脂肪酸的合成以及金黄色葡萄球菌的生长，而对肺炎链球菌的生长没有抑制作用。此外，与野生型菌株相比，这些化合物对过表达 fabI 的金黄色葡萄球菌的抗菌活性降低。这些结果表明，支链脂肪酸通过抑制体内 FabI 表现出抗菌活性。
