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一个基于tRNA修饰的调控策略,用于Streptomyces lincolnensis中林氏素生物合成

Yue Mao¹, Jiang Ye¹, Ruida Wang²

¹State Key Laboratory of Bioreactor Engineering, Department of Applied Biology, Bioengineering Experiment Teaching Demonstration Center, School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China.

Archives of microbiology

|January 12, 2026

概括

这项研究设计了tRNA修饰,通过克服罕见的UUA编码子来促进林科米辛抗生素的生产. 这种代谢工程策略增强了关键调节者的转化,改善了抗生素产量.

科学领域:

微生物生物技术微生物生物技术
分子生物学分子生物学
合成生物学合成生物学

背景情况:

作为一种关键的林科胺抗生素,林科素面临着生产限制,原因是基本调节蛋白中罕见的UUA编码子.
二次代谢物的有效生物合成往往是由它们的调节基因中罕见的密码子的存在阻碍的.

研究的目的:

开发一种通用的代谢优化策略,以提高林氏素的产量.
为了改造tRNA修改,以改进Streptomyces中罕见的编码体的解码.

主要方法:

联合过度表达UUA解码tRNA基因 (bldA) 和其修饰酶基因 (miaA).
使用相依赖促进体 (PlmbU) 控制 miaA 表达.
研究tRNA修饰对调控蛋白LmbU和AdpA的翻译的影响.

主要成果:

同时过度表达bldA和miaA显著增加了林氏素的产生.
在PlmbU下表达miaA进一步提高了抗生素产量.
该策略提高了UUA码头解码效率,导致LmbU和AdpA的更好的翻译.

结论:

tRNA修饰工程提供了一种新的方法来克服二次代谢物生产中的罕见代码子诱导的瓶.
这一策略可能适用于Streptomyces和其他相关物种中的其他罕见的依赖于codon的代谢物.
精确控制tRNA修饰提供了微生物代谢工程的合理基础.

关键词:

这种植物是Streptomyces lincolnensis.BldA 在AldA.林科米辛 (Lincomycin) 是一种药物.代谢工程是代谢工程.在tRNA修改过程中.

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