在Corynebacterium glutamicum中通过促进器工程和贝叶斯优化来增强L-氨酸的产生
Yujie Gao1,2, Anqian Liu3, Xiaomei Zhang4,5
1Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China.
World journal of microbiology & biotechnology
|June 24, 2025
概括
通过优化关键酶转录,为增强L-氨酸生产而改造的Corynebacterium glutamicum. 通过促进器工程和贝叶斯优化实现了创纪录的62.23 g/L L-氨酸标位.
科学领域:
- 生物技术是生物技术.
- 代谢工程是代谢工程.
- 微生物发酵 微生物发酵
背景情况:
- 氨酸是一种重要的氨基酸,在医学,食品和化品中具有应用.
- 科里尼细菌 (Corynebacterium glutamicum) 是一个成熟的宿主,用于工业氨基酸发酵.
- 提高C. glutamicum中的L-氨酸产量需要进行战略性遗传修饰.
研究的目的:
- 通过促进体工程来改善Corynebacterium glutamicum中的L-氨酸生产标位.
- 识别和利用强大的促进剂来调节L-氨酸合成基因 (serA,serC,serB) 的转录.
- 为了实现创纪录的L-氨酸发酵产量.
主要方法:
- 在C. glutamicum中评估了L-氨酸合成基因 (serA,serC,serB) 的原生和外源促进剂强度.
- 采用两步促进子替代策略来增强基因表达.
- 利用贝叶斯优化来进一步改善标位.
- 在5L发酵器中扩大发酵量.
主要成果:
- 促进剂强度分析显示P-serA:P-serC:P-serB的比率为101.70:1:7.69.
- 个体促进物替代剂增加了L-氨酸标位高达17.21% (A36-serA^dap-e11).
- 在ACB菌株中组合促进物替代产生了40.79g/L的L-氨酸 (33.43%的增加).
- 贝叶斯优化和发酵规模扩大导致最终标位为62.23g/L.
结论:
- 战略促进剂工程显著增强了C. glutamicum中的L-氨酸生物合成.
- 经过工程改造的ACB菌株表现出卓越的L-氨酸生产能力.
- 这项研究为通过C. glutamicum的发酵来生产L-胺树立了新的基准.
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