生物信息扩展和类抗生素的发现
Christopher J Schwalen1, Graham A Hudson1, Bryce Kille1
1Department of Chemistry , University of Illinois at Urbana-Champaign , 600 South Mathews Avenue , Urbana , Illinois 61801 , United States.
Journal of the American Chemical Society
|July 10, 2018
概括
研究人员通过分析细菌基因组,发现了许多新型抗生素. 他们还鉴定出一种独特的硫黄的生物合成途径,
科学领域:
- 自然产品化学
- 微生物学
- 生物信息学
背景情况:
- 硫是通过核糖体合成和翻译后修改的,具有强烈的抗菌作用,可对抗阳性细菌.
- 有几种类型的是用于兽医的工业生产,这突显了它们的治疗和经济重要性.
- 许多 thiopeptides 的生物合成途径仍然未知,限制了新类型的发现.
研究的目的:
- 通过使用生物信息学识别新的生物合成基因集群来扩大已知的类.
- 隔离和描述一种具有独特结构特征和强大的抗生素活性的新.
- 阐明对 thiopeptides 中的 thioamide 部分负责的翻译后修饰途径.
主要方法:
- 使用定制生物信息学程序 (RODEO) 对细菌基因组进行大规模分析,以识别类生物合成基因集群.
- 采用全基因组测序,比较基因组学和异质表达来表征新型硫黄及其生物合成途径.
- 隔离并确定了萨尔费尔杜拉辛的结构,包括其独特的piperidine和thioamide部分.
主要成果:
- 扩大了已知的二家族的四倍,确定了许多新的基因和以前未被指定的特征分子.
- 隔离和特征萨尔费尔杜拉辛,一种具有中心皮佩里丁和胺部分的新型,对抗药物耐药的格拉姆阳性病原体表现出强烈活性.
- 证实胺部分通过TfuA和YcaO的联合作用在翻译后安装,澄清了已知胺中这种修饰的起源.
结论:
- 这项研究显著扩大了的化学基因空间,揭示了大量未被发现的自然产物.
- 萨尔费尔杜拉辛是一种有前途的新型抗生素化合物,对抗耐药细菌具有活性.
- 阐明的生物合成途径为设计具有定制性质的新型提供了基础,并发现了额外的家族成员.
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