重新利用内源型I-E CRISPR-Cas系统,用于在Streptomyces中发现天然产品
Qun Zhou1,2, Yatong Zhao1,2, Changqiang Ke3
1Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
Nature communications
|November 13, 2024
概括
科学家们开发了基于CRISPR的新工具,以激活Streptomyces细菌中隐藏的天然产品基因集群. 这种方法成功地发现了新型化合物,扩大了从这些微生物中发现药物的潜力.
科学领域:
- 微生物学和生物技术
- 分子生物学分子生物学
- 自然产品的发现自然产品的发现
背景情况:
- 菌群Streptomyces细菌在其生物合成基因集群 (BGCs) 中拥有一个庞大的,未被探索的自然产品储备.
- 以前的基于CRISPR的方法,主要使用Cas9等2类系统,对于大多数Streptomyces菌株来说,BGC激活并不普遍.
- 第1类CRISPR系统,特别是I-E类型,在Streptomyces中普遍存在,并为基因操纵提供了替代平台.
研究的目的:
- 将I-E型CRISPR系统改造为Streptomyces的多功能转录调节工具.
- 为了证明这些新型工具在各种Streptomyces物种中的广泛适用性和有效性.
- 激活神秘的BGC,并从Streptomyces中发现新的天然产品.
主要方法:
- 开发I-E型CRISPR衍生的转录激活剂.
- 将这些工具应用于九个分类基因上不同的Streptomyces菌株.
- BGCs的激活和随后的生产自然产品的识别和表征.
主要成果:
- 成功开发和验证了基于CRISPR的I-E型转录调节工具.
- 证明了这些工具在激活多个Streptomyces菌株的BGCs方面的有效性.
- 在21个向的BGC中激活了13个,从而发现了一个多基化物,一个RiPP和三个类化合物.
结论:
- 类型I-E的CRISPR系统可以有效地作为Streptomyces的转录激活剂重新使用.
- 这种新的方法显著提高了访问和发现Streptomyces神秘天然产品的能力.
- 预计开发的工具将加速发现结构多样化的化合物,影响天然产品研究.
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