一本关于基因组挖掘和Streptomyces生物合成基因集群的基因操纵的指南
Heonjun Jeong1, YeonU Choe1, Jiyoon Nam1
1Department of Intergrative Molecular and Biomedical Science, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
Journal of microbiology (Seoul, Korea)
|May 2, 2025
概括
菌群Streptomyces细菌含有许多沉默的基因集群,有可能制造新药. 本指南详细介绍了使用抗SMASH和基因编辑来解锁这些静默的生物合成基因集群,并发现新的天然产品.
科学领域:
- 微生物学 微生物学
- 基因组学就是基因组学.
- 自然产品的发现自然产品的发现
背景情况:
- 杆菌细菌是具有临床意义的生物活性二次代谢物的丰富生产者.
- 基因组研究揭示了Streptomyces中众多未经表征的,沉默的生物合成基因集群 (BGC),代表了新型自然产品发现的未开发潜力.
- 目前用于识别和激活这些沉默的BGC的方法对于扩大治疗性天然产品的剧目至关重要.
研究的目的:
- 通过使用反SMASH管道,提供一个全面的,逐步的协议,用于识别Streptomyces基因组中的二次代谢物BGC.
- 概述用于激活神秘BGC和验证Streptomyces基因功能的基因操纵技术.
- 为了促进新型,治疗性相关的自然产品从Streptomyces的发现和表征.
主要方法:
- 使用反SMASH管道识别新型Streptomyces基因组中的BGCs的基因组挖掘.
- 应用基因操纵技术来激活沉默的BGCs.
- 通过针对性基因编辑和分析验证生物合成基因功能.
主要成果:
- 通过使用antiSMASH在目标Streptomyces基因组中成功识别了包括静态基因在内的众多BGC.
- 演示了激活特定神秘BGCs的方法,从而有可能产生新型化合物.
- 建立工作流程,将已识别的BGC与其编码的产品联系起来,并进行功能验证.
结论:
- 提出的协议有效地利用基因组挖掘和基因操纵来释放Streptomyces中沉默的BGCs的潜力.
- 这种方法显著增强了具有治疗应用的新生物活性二次代谢物的发现管道.
- 提供的指导方针将有助于研究人员从尚未探索的Streptomyces基因集群中描述有价值的天然产品.
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