促进器工程使精确的新陈代谢调节能够在Ogataea polymorpha中实现高效的β元素生产
Min Ye1,2, Jiaoqi Gao1,3,4, Jingjing Li1,4
1Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023, PR China.
Synthetic and systems biotechnology
|February 22, 2024
概括
研究人员扩展了Ogataea polymorpha中的促进子库,从而实现了精确的基因控制,以增强生物合成. 这导致了使用工程酵母细胞工厂显著增加β元素的生产.
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:
- 在非传统的酵母中,如Ogataea polymorpha中,促进剂的有限可用性阻碍了优化生物合成途径的精确基因调制.
- 开发多样化的促进子集对于微调基因表达和构建高效的微生物细胞工厂至关重要.
研究的目的:
- 通过表征构成性和生长阶段依赖性促进体,扩大O. polymorpha中的促进体库.
- 为了改进基因表达控制,设计具有增强活性的新型混合促进剂.
- 应用促进器工程来精确调节新陈代谢,以增强β元素的产生.
主要方法:
- 转录数据分析以识别和表征O. polymorpha.中的新促进体.
- 构建和表征混合生长阶段依赖的促进者.
- 代谢工程策略包括基因下调 (GAP) 和通路构造 (PK-PTA) 与相依基因表达相结合.
主要成果:
- 建立了13个构成性促进者 (0-55%的P_GAP强度) 和2个依赖生长阶段的促进者的图书馆.
- 两种新型混合促进剂的活性高达现有促进剂的两倍.
- 工程菌株YY150U通过食批发发酵实现了贝塔基素最高标位5.24g/L,产量为0.037g/g葡萄糖.
结论:
- 扩展和改造的促进子集为O. polymorpha.中微调基因表达提供了必要的工具.
- 通过促进体工程精确的代谢调节显著增强了β元素的产生.
- 这项工作有助于为工业应用开发高效的酵母细胞工厂.
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