重写酵母中枢碳代谢,用于工业化异烯酸生产
Adam L Meadows1, Kristy M Hawkins1, Yoseph Tsegaye1
1Amyris, 5885 Hollis Street, Suite 100, Emeryville, California 94608, USA.
Nature
|September 23, 2016
概括
工程酵母现在可以生产25%更多的β-法, 这种新陈代谢的重新连接使得价值的化学物质能够在经济高效的大规模生物生产.
科学领域:
- 代谢工程
- 合成生物学
- 工业生物技术
背景情况:
- 生物经济的发展需要可持续的石油产品替代品.
- 在此之前,Saccharomyces cerevisiae 已经被设计成用于酸的生产,但其原生异基路径限制了工业的可扩展性.
- 贝塔法尼 (C15H24) 是一种基,具有多种工业应用,但在酵母中面临生产挑战.
研究的目的:
- 通过优化中央碳代谢来增强Saccharomyces cerevisiae中的β-法内森的产生.
- 提高乙辅酶A (乙-CoA) 生物合成的效率,这是异类的关键前体.
- 克服产量,生产力和工业规模发酵氧气需求的局限性.
主要方法:
- 在S. cerevisiae中使用四种非本地代谢反应重新连接中央碳代谢.
- 增强细胞酸乙-CoA生产的工程,减少ATP和CO2的损失.
- 改善氧化还原路径,以提高生物合成效率.
- 在工业发酵条件下评估工程菌株的性能.
主要成果:
- 与对照品种相比,改造酵母菌株从相同的糖量中产生25%的β-法内森.
- 改造后的菌株需要75%的氧气,大大降低了发酵成本.
- 在工业条件下维持了两周的强生长和稳定的β-法产量 (体积≥15%).
- 降低了对ATP的需求和二氧化碳的损失.
结论:
- 重新连接酵母的中央新陈代谢是一种可行的策略,用于经济高效的大规模生产乙-CoA衍生分子,如β-farnesene.
- 改造后的菌株表现出更高的效率和适合工业应用的生产力.
- 这种方法为生产有价值的化学品提供了可持续的替代方案,减少了对石油的依赖.
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