通过高能电子束诱导的强烈结构变化来增强微生物的代谢能力
Xinyuan Feng1, Zilong Li2, Yifei Zhang3
1Department of Gastroenterology of the Second Affiliated Hospital and Institute of Pharmaceutical Biotechnology, School of Medicine, Zhejiang University, Hangzhou, China.
Nature communications
|February 19, 2026
概括
高能脉冲电子束 (HEPE) 在微生物中有效诱导DNA双链断裂 (DSB) 和结构变异 (SV). 这种方法增强了代谢物生产,并有助于发现新的药物化合物.
科学领域:
- 微生物生物技术 微生物生物技术
- 基因组学和基因工程学
- 代谢学和自然产品的发现.
背景情况:
- 小分子代谢物是重要的制药资源,需要可扩展的微生物生产.
- 有效的遗传变异,特别是结构变异 (SVs),对于微生物菌株的改善至关重要,但很难诱导.
- 现有的突变发生法方法努力平衡DNA双链断裂 (DSB) 诱导与细胞保存,以提高代谢物产量.
研究的目的:
- 系统地比较六种辐射技术,用于诱导微生物菌株的遗传变异.
- 确定一种有效诱导DSB和SV的方法,同时保持细胞完整性,以改善代谢物生产.
- 利用这种方法发现新的二次代谢物并提高已知的化合物的产量.
主要方法:
- 在Streptomyces lividans 1326中对六种辐射技术进行系统比较.
- 识别和应用高能脉冲电子束 (HEPE) 来诱导DSB和SV.
- 整合HEPE与高通量代谢学 (HEPE-HiTMS) 进行代谢物分析和发现.
主要成果:
- 高能脉冲电子束 (HEPE) 被确定为诱导DSB和广泛的SV的有效方法,细胞毒性最小.
- HEPE治疗重塑了基因组序列和3D染色质结构,导致激活的二次代谢产物.
- 通过HEPE-HiTMS,发现了两种新型的二次代谢产物,具有不寻常的C-N链接,并显著增加了克拉酸,微J25和洛瓦斯塔丁的产量.
结论:
- HEPE是一种强大的工具,用于诱导高效率和低细胞毒性SVs,超过传统方法.
- 这项技术显著提高了用于工业代谢物生产的微生物菌株的发展.
- HEPE促进了神秘的代谢物发现,并加速了微生物细胞工厂的发展.
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