将比较基因组学与串联的基于质量的分子网络结合起来,可以高效地发现来自诺卡迪亚 spp 的非核糖体
Shanshan Chang1, Yajun Luo2, Mengyuan Wang1
1CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tiantan xili No.1, Beijing, 100050, China.
Journal of chromatography. A
|September 17, 2023
概括
这项研究引入了一种结合基因组学和质谱学的新战略,从诺卡迪亚细菌中发现新的微生物自然产物,特别是非核糖体 (NRPs),克服复合物重新发现的挑战.
科学领域:
- 微生物学 微生物学
- 自然产品 化学 化学
- 基因组学就是基因组学.
背景情况:
- 微生物天然产品,特别是非核糖体 (NRPs),由于其多样化的结构和治疗潜力,对药物发现有价值.
- 诺卡迪亚细菌是这些化合物的丰富来源,但已知代谢物的重新发现阻碍了新发现的新代谢物的识别.
- 需要有效的策略来从微生物基因组中挖掘新的专门代谢物.
研究的目的:
- 开发和验证一项战略,以有效地从诺卡迪亚物种中发现新的非核糖体 (NRPs).
- 为了克服天然产品采矿中复合物重新发现的挑战.
- 将已识别的化合物与其特定的生物合成基因集群联系起来.
主要方法:
- 用比较基因组学来识别诺卡迪亚菌株中独特的生物合成基因集群 (BGCs).
- 基于串联质谱的分子网络被用来分析代谢学数据.
- 生物信息学分析被用来提出生物合成途径并确认BGCs.
主要成果:
- 该策略成功地确定了一种已知的脂,诺卡贾米德和五种新的同源物.
- 此外,还发现了一种新型的脱卡利波胺,诺卡利波胺和一种已知的化合物,诺卡尔迪米辛.
- 使用NMR,MS/MS,Marfey分析和X射线晶体学,广泛描述了新型decalipopeptide的结构.
- 确认了生物合成途径和对已识别的化合物负责的基因集群.
结论:
- 对比基因组学和分子网络的结合方法使已知的化合物能够快速地复制.
- 这一策略有助于有效地将已识别的代谢物与其生物合成基因集群联系起来.
- 开发的方法显著提高了从诺卡迪亚物种中发现新型非核糖体的发现.
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