通过防止 propionate 诱导的生长抑制,改善了 C. glutamicum 中的多基化物生产
Chunjun Zhan1,2,3, Namil Lee1,2,3, Guangxu Lan1,2
1Joint BioEnergy Institute, Lawrence Berkeley National Laboratory, Emeryville, CA, USA.
Nature metabolism
|July 13, 2023
概括
添加 Propionate 通过积累特定的代谢物来抑制 Corynebacterium glutamicum 的生长. 这种抑制可以通过引入多基化合成酶来克服,通过适应性进化实现增强的细菌素生产.
科学领域:
- 微生物生物技术 微生物生物技术
- 代谢工程是代谢工程.
- 合成生物学 合成生物学
背景情况:
- 谷氨酸菌 (Corynebacterium glutamicum) 是一种重要的工业微生物,用于生产有价值的化合物.
- 氨酸补充剂通过增加甲基马洛尼尔-CoA来增强聚基胺合成,但会导致显著的生长抑制.
- 在C. glutamicum中,酸诱导的增长抑制背后的精确机制在很大程度上是未知的.
研究的目的:
- 阐明C. glutamicum中酸诱导的生长抑制机制.
- 开发克服这种抑制和增强聚基化物生产的战略.
- 使用适应性实验室进化来改善C. glutamicum中细菌素的产生.
主要方法:
- 代谢物分析以识别在 propionate 压力下积聚的化合物.
- 基因工程引入依赖甲基-CoA的多基基合成酶.
- 适应性实验室进化 (ALE) 结合全基因组测序.
主要成果:
- 鉴定出propionyl-CoA和methylmalonyl-CoA的积累是抑制生长的原因.
- 引入依赖甲基马洛尼尔-CoA的多基化合成酶缓解了生长抑制.
- ALE导致细菌素的产生改善,并揭示了细菌素合成酶和酸盐合成酶的突变,改变了glyoxylate到甲基酸盐的途径.
结论:
- C. glutamicum可以被设计为高效的多基化物生产.
- 酸诱导的生长抑制可以在战略上被用来改善和发现菌株.
- 适应性进化提供了一种强大的工具,可以增强多基酸标位,并在C. glutamicum中改造代谢途径.
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