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阴酸,来自土壤元基因组的依赖的酸性脂,对抗多药耐药细菌具有活性
Changsheng Wu1, Zhuo Shang1, Christophe Lemetre1
1Laboratory of Genetically Encoded Small Molecules , The Rockefeller University , New York , New York 10065 , United States.
Journal of the American Chemical Society
|February 9, 2019
概括
研究人员发现了新的依赖的抗生素,酸,对抗耐药细菌有效. 这些新型脂破坏细胞壁生物合成,为抗生素耐药性提供了有前途的途径.
科学领域:
- 微生物学 微生物学
- 生物化学 生物化学
- 药物发现 药物发现 药物发现
背景情况:
- 抗生素耐药性是一个日益增长的全球健康威胁.
- 依赖的抗生素是一种利波类抗生素,具有针对耐药病原体的多种机制.
- 非核糖体合成酶 (NRPSs) 是它们组装的关键.
研究的目的:
- 识别和描述新的依赖的抗生素.
- 探索发现抗生素活性抗耐药病原体的新策略.
- 为了研究地表生产的遗传基础.
主要方法:
- 使用NRPS腺化 (AD) 域测序来识别基因集群.
- 甲基因组DNA进行了选,以恢复cde生物合成基因集群.
- 异质表达被用来产生和分析化合物.
主要成果:
- 鉴定了cde基因集群,并从土壤元基因组中克隆.
- 产生了两种新的酸性脂,分别是A和B类基.
- 化物表现出独特的结构,通过破坏细胞壁生物合成来抑制多抗药性格拉姆阳性病原体.
- 在富含的土壤中,样基因集群很普遍.
结论:
- 类抗生素 (Cadasides) 是一种新的依赖的抗生素子家族.
- 这些化合物显示出治疗多药耐药细菌引起的感染的潜力.
- 这些发现突显了NRPS测序对抗生素发现的有用性,并表明了 cadaside生物合成和碳酸水平之间的环境联系.
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