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通过在蛋白质细菌中的非核糖体合成酶的启动单元工程来访问未被探索的生物合成潜力

Xianping Bai¹, Lin Zhong², Yang Liu¹

¹Helmholtz International Lab for Anti-Infectives, State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237, China.

Journal of the American Chemical Society

|February 18, 2026

概括

研究人员通过更换启动单元来设计非核糖体合成酶 (NRPSs). 这一策略激活了无声的NRPS通路,产生了新型脂,并使细菌能够在细菌中人工产生脂.

科学领域:

生物化学生物化学
合成生物学合成生物学
自然产品的发现自然产品的发现

背景情况:

非核糖体合成酶 (NRPS) 是产生生物活性天然产品的强大工具.
许多NRPS通道保持沉默,限制了它们的实用性,通常是由于启动单元的问题.
启动凝结 (Cs) 域通过添加一个N端脂肪酸链来启动脂启动.

研究的目的:

通过启动单元工程来开发激活静音NRPS通路的策略.
通过访问以前被沉默的NRPS集群来发现新的脂.
通过将脂肪酸链结合到非核糖体中来制造人工脂.

主要方法:

启动单元工程:用外国的Cs域含有单元取代本地启动单元.
在*Mycetohabitans rhizoxinica* (β-蛋白细菌) 中应用,以激活静音NRPS通路.
扩展到*Pseudomonas syringae* (γ-蛋白质细菌) 和非脂质通路的工程.

主要成果:

在*M. rhizoxinica*中成功激活了三个静态NRPS通路,确定了三类脂.
在 *P. syringae* 中访问了两个NRPS通路,发现了新的脂.
通过将脂肪酸链结合到非脂质脊髓中,证明了人造脂的产生.

结论:

启动单元工程是激活无声NRPS基因集群 (BGCs) 的实用策略.
这种方法促进了新脂的发现和人工脂的创造.
该方法增强了NRPS衍生的天然产品的基因组挖掘和组合生物合成,特别是在蛋白质细菌中.

关键词:

组合生物合成的组合生物合成启动单位是一个启动单元.脂类是脂类中的一种.非核糖体合成酶非核糖体合成酶启动凝结域是一个启动凝结域.

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