重编程酵母的碳新陈代谢,以过度生产甲酸盐,这是形脊柱的前身
Ge Zhang1,2, Yurui Ma3, Meina Huang4
1Key Laboratory of Engineering Biology for Low-Carbon Manufacturing, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
Journal of agricultural and food chemistry
|December 17, 2024
概括
在Yarrowia lipolytica中,通过优化美酸盐路径和中央碳代谢,增强了微生物类的产生. 这项研究实现了创纪录的101g/L的美瓦酸盐位,为可持续的生物化学生产铺平了道路.
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:
- 自然植物产品的微生物生产为传统方法提供了一个可持续的替代方案.
- 类的高效生物合成是关键的自然产品,在微生物系统中面临着挑战.
- 雅罗维亚 (Yarrowia lipolytica) 是一个有前途的宿主,可以生产有价值的化合物.
研究的目的:
- 为了识别和克服Yarrowia lipolytica中类生物合成的代谢约束.
- 为了优化梅瓦酸盐的生产,这是类的关键前体.
- 建立一个强大的微生物平台,用于高度的生物化学生产.
主要方法:
- 通过调节ERG12和HMGR表达来设计了美酸盐 (MVA) 途径.
- 通过酸盐路线和TCA循环工程增强了本地MVA通路,并优化了通过酸盐路线和TCA循环工程来供应乙-CoA.
- 通过删除CEX1以最大限度地提高美酸盐生产,消除了酸盐溢流代谢.
主要成果:
- 通过初始途径调节,实现了美瓦酸标位的7660%的改善.
- 通过增强MVA通路,增加了美酸盐的产量,达到4.16g/L.
- 通过对中央碳代谢进行工程,进一步提高了mevalonate标位到5.25g/L.
- 通过消除酸盐溢出,达到创纪录的美瓦酸盐位101g/L,产量为0.255g/g葡萄糖.
结论:
- 代谢工程策略显著提高了Yarrowia lipolytica中的美酸盐产量.
- 优化前体供应和消除代谢副产品对于高滴度生物合成至关重要.
- 开发的平台为可持续生产类和其他有价值的生物化学品提供了基础.
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