无细胞生物合成和 ribosomally 合成 lanthipeptides 的工程
Wan-Qiu Liu1, Xiangyang Ji1, Fang Ba1
1School of Physical Science and Technology, ShanghaiTech University, Shanghai, China.
Nature communications
|May 21, 2024
概括
一个新的无细胞系统,UniBioCat,能够快速生物合成和 ribosomally合成和后翻译修饰 (RiPPs) 的工程. 这个系统加速了发现和描述具有潜在生物活动的新型RiPPs.
科学领域:
- 生物化学 生物化学
- 合成生物学 合成生物学
- 自然产品 化学 化学
背景情况:
- 核糖体合成和翻译后改性 (RiPPs) 是一个庞大,多样化的自然产品类别,具有显著的生物活性.
- 许多RiPP基因集群由于当前异质表达系统对高效生物合成和分析的局限性而没有表征.
- 开发快速有效的系统对于探索RiPPs的巨大潜力至关重要.
研究的目的:
- 开发一个统一的生物催化剂 (UniBioCat) 系统,用于使用无细胞基因表达的RiPPs的快速生物合成和工程.
- 通过重建沙利瓦辛B生物合成途径和工程变体来证明系统的能力.
- 建立UniBioCat系统对其他RiPPs,特别是兰氏的通用性.
主要方法:
- 利用无细胞基因表达平台建立了UniBioCat系统.
- 重建了兰氏RiPP的完整生物合成途径,沙利瓦辛B.
- 通过删除蛋白酶/酶基因来设计该系统,并将其应用于合成和选沙利瓦里B变体.
- 通过合成和评估十种未经表征的兰氏来验证系统的多功能性.
主要成果:
- 成功建立并演示了UniBioCat系统,用于新增生物合成西利瓦辛B.
- 通过修改源菌株来提高UniBioCat的性能,使得沙利瓦里B变体的合成和选能够提高抗菌活性.
- 通过成功合成和评估十种多样化,不具特征的兰氏的生物活性,证实了UniBioCat的可通用性.
结论:
- UniBioCat系统为RiPPs的无细胞生物合成和工程提供了一个快速高效的平台.
- 该系统显著加速了新型RiPP及其变体的发现,表征和合成探索.
- 预计UniBioCat将成为解锁广的RiPP景观的化学多样性和生物潜力的宝贵工具.
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