通过代谢工程化大肠杆菌对1,5-二醇进行De Novo生物合成
Chen Ma1, Lisha Qin1, Wenfeng Hua1
1State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, Jiangsu, China.
Biotechnology and bioengineering
|February 5, 2026
概括
这项研究设计了一个高效的微生物工厂,使用大肠杆菌生产1,5-二醇 (1,5-PDO). 改造品种实现了12.9g/L的创纪录产量,大大减少了中间积累,以改善化学合成.
科学领域:
- 生物技术是生物技术.
- 代谢工程是代谢工程.
- 合成生物学 合成生物学
背景情况:
- 1,5-二醇 (1,5-PDO) 是聚合物的宝贵化学原料.
- 目前用于1,5-PDO的新合成方法存在中期积累和低产量问题.
- 开发高效的微生物生产途径对于可持续的化学制造至关重要.
研究的目的:
- 为1,5-二醇 (1,5-PDO) 的生物合成设计一个高效的微生物细胞工厂.
- 为了优化生产途径,并最大限度地减少5-基酸 (5-HV) 的积累.
- 为了在大肠杆菌中获得1,5-PDO的高产量.
主要方法:
- 在l-lysine产生的大肠杆菌中设计了一个微生物细胞工厂,配备了5-二 (5-HV) 和1,5-PDO合成模块.
- 选和组合关键酶 (MmCAR,Yahk,GabT) 以获得最佳的1,5-PDO合成.
- 采用蛋白质工程 (MmCARQ302E变种),RBS工程,蛋白质支架 (EutM) 和基因删除 (ycjQ) 进行途径优化.
- 优化发酵条件以最大限度地提高1,5-PDO产量.
主要成果:
- 确定了1,5-PDO生物合成的最佳酶组合 (MmCAR,Yahk,GabT).
- 设计了MmCARQ302E变种,以增强5-HV转换并减少中间积累.
- 通过增强的CAR表达和EutM支架,进一步减少了5-HV积累.
- 删除了内源的ycjQ基因以防止1,5-PDO再氧化.
- 在最佳的发酵条件下实现了12.9g/L的1,5-PDO纪录产量.
结论:
- 成功建立了一家高效的微生物细胞工厂,用于在大肠杆菌中进行1,5-PDO生物合成.
- 证明了合理的酶工程,途径优化和发酵控制可以显著提高产品产量并减少副产品.
- 取得的产量代表了1,5-PDO微生物生产的重大进步,为其可持续的工业应用铺平了道路.
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