Antibacterial Cyclic Lipopeptide Enamidonins with an Enamide-Linked Acyl Chain from a Streptomyces Species
Antibacterial Cyclic Lipopeptide Enamidonins with an Enamide-Linked Acyl Chain from a Streptomyces Species
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DOI：
10.1021/acs.jnatprod.8b00497
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发表时间：
2018-11-01
影响因子：
5.1
通讯作者：
Ahn, Jong Seog
中科院分区：
文献类型：
--
作者：
Son, Sangkeun;Ko, Sung-Kyun;Ahn, Jong Seog
从放线菌Streptomyces sp. KCB 14 A132中发现了三种具有稀酰胺键的环状脂肽，包括一种已知化合物（1）和两种新化合物（2和3）。基于NMR和MS的表征表明，它们在肽骨架中的氨基酸残基不同。应用Marvelt分析、GITC衍生化和改进的Mosher方法以及ECD测量提供了enamidonin（1）和新化合物enamidonin B和C（2和3）的绝对构型。这两个新的enamidonin类似物显示出对革兰氏阳性菌包括耐甲氧西林和耐喹诺酮金黄色葡萄球菌的抗菌活性。此外，对提取条件的评价和LC-MS色谱图的仔细检查显示，在丙酮提取过程中形成了enamidonin家族的N，N-丙酮化合物单元。发现化学制备的enamidonins的去丙酮衍生物缺乏抗菌活性，表明二甲基咪唑烷酮残基是抗菌活性所必需的。
Three cyclic lipopeptides, including one known (1) and two new (2 and 3) compounds, that possess the rare enamide linkage group were discovered from Streptomyces sp. KCB14A132, an actinobacterium isolated from a soil sample collected from Jeung Island, Korea. The NMR and MS-based characterization showed that they differed in the amino acid residues in the peptide backbone. Application of Marfey's analysis, GITC derivatization, and modified Mosher's method, as well as ECD measurements provided the absolute configurations of enamidonin (1) and those of new compounds enamidonins B and C (2 and 3). The two new enamidonin analogues were shown to exhibit antibacterial activity against Gram-positive bacteria including methicillin-resistant and quinolone-resistant Staphylococcus aureus. Furthermore, evaluation of the extraction conditions and a close inspection of the LC-MS chromatograms revealed that the N,N-acetonide unit of the enamidonin family was formed during the acetone extraction process. The chemically prepared deacetonide derivatives of enamidonins were found to lack antibacterial activity, demonstrating that the dimethylimidazolidinone residue is necessary for antibacterial activity.