核糖体合成的硫类抗生素,向延长因子Tu
Rowan P Morris1, Jennifer A Leeds, Hans Ulrich Naegeli
1Natural Products Unit, Novartis Institutes for BioMedical Research, Basel, 4056, Switzerland.
Journal of the American Chemical Society
|April 3, 2009
概括
发现了一种罕见的细菌的新型硫类抗生素 - - 硫素. 它们针对细菌延长因子Tu (EF-Tu),提供一种新的策略来对抗具有较低抗性潜力的金黄色葡萄球菌.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 硫是一种宏环,高度修饰的类,具有中心的异环环系统.
- 铁类抗生素是通过核糖体合成和染色体编码的.
- 许多 thiopeptides 的生物合成途径仍然难以捉摸.
研究的目的:
- 为了识别针对金黄色葡萄球菌的新型抗生素.
- 为了阐明一种新的 thiopeptide 家族, thiomuracins 的生物合成路径.
- 为了确定thiomuracins的分子标和耐药性概况.
主要方法:
- 检查罕见的菌细菌的抗菌活性,以检测它们对金黄色葡萄球菌的抗菌活性.
- 基因组采矿用于识别类基因集群.
- 生物化学分析以确定蒂奥穆拉辛的标.
- 细菌耐药性选择试验. 细菌耐药性选择试验.
主要成果:
- 鉴定thiomuracins,一种来自Nonomuraea物种的新型 thiopeptide 家族.
- 对 thiomuracins 和相关 thiopeptides 的生物合成途径的解.
- 确定蒂奥穆拉辛向细菌延长因子Tu (EF-Tu).
- 蒂奥穆拉辛对黄金葡萄球菌具有强烈的活性,对耐药性发展的倾向较低,与现有的抗生素没有交叉耐药性.
结论:
- 蒂奥穆拉辛是一种有前途的新型抗生素,针对未开发的细菌机制.
- 这一发现为蒂奥胺生物合成提供了洞察力,并为设计新型抗生素提供了潜力.
- 蒂奥穆拉辛为对抗抗生素耐药性细菌感染提供了潜在的解决方案.
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