开发一种基于基数感应的内生双功能动态调节系统,用于在Streptomyces中高效的产品合成
Mengyao Yang1, Yifan Zhao1, Ruihui Huang1
1State Key Laboratory of Animal Biotech Breeding and College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Bioresource technology
|June 28, 2025
概括
科学家们在Streptomyces avermitilis中设计了一种新的系统,以动态控制基因表达,以增加阿维美克丁的产生. 这种双功能动态调节在野生型和工业型菌株中显著提高了avermectin B1a的产量.
科学领域:
- 微生物学 微生物学
- 合成生物学 合成生物学
- 代谢工程是代谢工程.
背景情况:
- 杆菌种类是有价值的二次代谢产物的丰富生产者,包括像阿弗梅克丁 (AVE) 这样的抗生素.
- 由于缺乏灵活,动态的基因调控工具,工程化Streptomyces菌株具有挑战性.
- 现有的定数感应 (QS) 系统缺乏同时上下调节各种基因组的能力,以优化产品合成.
研究的目的:
- 在Streptomyces avermitilis.中设计和实施一个双功能动态基因调节系统.
- 为了利用内源的阿维诺利德介导的QS系统来精确控制基因表达.
- 通过动态调节代谢途径来增强阿弗梅克丁的产生.
主要方法:
- 设计了一个双功能动态调节系统,利用内源的阿维诺利德介导的QS电路.
- 采用动态上调调节来增强AVE合成的前体供应基因.
- 使用动态下调来重定向代谢流量,通过向TCA循环中的关键基因,酸盐降解和酸盐合成途径.
主要成果:
- 前体基因的上调导致野生型 (WT) 菌株AVE B1a标位增加727.4%.
- 代谢节点基因的下调导致WT菌株B1a标位增加了589.6%.
- 两种电路的联合应用实现了显著的B1a度增加:比WT高858.1%,比高产量的工业菌株高25.7%.
结论:
- 开发了一种新的双功能动态调节策略,用于改善微生物菌株.
- 证明了该系统在显著增强阿维尔麦克丁产量的有效性.
- 该策略有可能广泛适用于具有已识别的内源性QS系统的其他微生物.
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