通过CRISPRi介导的代谢开关可以在工程化联盟中同时进行有氧和合成无氧发酵
Yixin Rong1, Adrian Frey1, Emre Özdemir1
1The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Nature communications
|October 17, 2024
概括
这项研究引入了一种用于可持续生物制造的新型发酵平台. 它使用单个生物反应器中的工程细菌产生有价值的化合物,提高效率和经济可行性.
科学领域:
- 生物技术和代谢工程 生物技术和代谢工程
- 可持续的化学制造 可持续的化学制造
- 合成生物学 合成生物学
背景情况:
- 石油化工的依赖需要基于生物的替代品来实现可持续发展.
- 生物制造的经济可行性需要优化微生物菌株和工艺.
- 目前的方法往往涉及多个,连续的发酵步骤.
研究的目的:
- 开发一个创新的发酵平台,在单个生物反应器中实现两个并发发酵.
- 设计大肠杆菌菌株以高效生产生物基化合物和副产品的共同利用.
- 提高生物化学生产的经济可行性.
主要方法:
- 使用CRISPRi介导的基因沉默来控制新陈代谢,构建一种产生西利的大肠杆菌菌株.
- 通过基于约束的代谢建模设计的第二个大肠杆菌菌株的工程,以共同代谢葡萄糖和酸盐.
- 在单个生物反应器内实施同步发酵的合成微生物联盟.
主要成果:
- 改造的大肠杆菌菌株在氧气条件下成功将新陈代谢转换为无氧条件,将生长与生产脱,并增加产量.
- 二级大肠杆菌菌株有效地共同代谢葡萄糖和酸盐,这是第一个菌株的副产品.
- 在一个生物反应器中的并发发酵实现了与两个单独的单菌株发酵相比的标位和生产率.
结论:
- 开发的发酵平台可以实现高效,并发的生物制造工艺.
- 这种综合性联盟方法提供了一个可行的战略,以提高生物化学品的经济竞争力.
- 该研究表明,微生物细胞工厂优化在可持续化学生产方面取得了重大进展.
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