超越CEN.PK - 精选的S. cerevisiae菌株的并行工程揭示了优越的底盘菌株需要不同的工程方法来生产利蒙
Yanmei Zhu1, Sasha Yogiswara1, Anke Willekens1
1VIB - KU Leuven Center for Microbiology, Gaston Geenslaan 1, 3001, Leuven, Belgium; CMPG Laboratory of Genetics and Genomics, Department M2S, KU Leuven, Gaston Geenslaan 1, 3001, Leuven, Belgium.
Metabolic engineering
|May 7, 2025
概括
我们优化了Saccharomyces cerevisiae菌株以生产利蒙,通过选择坚固的菌株和量身定制代谢工程来实现更高的标位. 这凸显了菌株多样性对工业生物生产的重要性.
科学领域:
- 合成生物学 合成生物学
- 代谢工程是代谢工程.
- 微生物生物生产 微生物生物生产
背景情况:
- 基因工程微生物对于生产有价值的化合物至关重要.
- 目前的方法通常依赖于有限的,非优化的微生物菌株.
- 工业强度和高位数对于生物工艺的可行性至关重要.
研究的目的:
- 识别和优化Saccharomyces cerevisiae底盘菌株,以提高利蒙的生产.
- 为了利用高通量选和并行代谢工程来改善菌株.
- 为了研究单二烯生物生产的菌株特定代谢工程策略.
主要方法:
- 选了921种不同的Saccharomyces cerevisiae菌株,以检测它们的烯耐受性和脂质含量.
- 评估了16种植物里蒙合成酶,以获得最佳的酶活性.
- 应用了并行代谢工程和针对菌株的优化,对美瓦酸路径.
- 利用代谢分析来了解特定菌株的性能差异.
主要成果:
- 确定了两种S. cerevisiae菌株,其胺位比标准CEN. PK2-1C菌株高2倍.
- 证明了最佳的工程策略是依赖应变的,与本地美酸盐生产有关.
- 在一个优化的菌株中获得了最终844mg/L的利蒙烯标位,比CEN.PK2-1C (605mg/L) 增加了40%.
结论:
- 在S. cerevisiae中的遗传多样性可以有效地用于改善单烯生物生产.
- 针对特定微生物菌株量身定制代谢工程方法,对于最大限度地提高产量标位至关重要.
- 这项工作为优化使用多种微生物底盘的其他高价值化合物提供了一个框架.
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