重新编程Yarrowia lipolytica的新陈代谢,以便有效地从瓶中合成伊塔克酸,并将其转化为半飞行员尺度
Jing Fu1,2, Simone Zaghen1, Hongzhong Lu3
1Division of Systems and Synthetic Biology, Department of Life Sciences, Chalmers University of Technology, Göteborg 412 96, Sweden.
Science advances
|August 9, 2024
概括
这项研究设计了安全的酵母Yarrowia lipolytica用于生产伊塔康酸,克服了真菌病原体Aspergillus terreus的局限性. 优化发酵实现了高伊塔克酸标位,使得具有竞争力的工业规模制造成为可能.
科学领域:
- 生物技术是生物技术.
- 代谢工程是代谢工程.
- 工业微生物学 工业微生物学
背景情况:
- 伊塔科尼酸是一种有价值的平台化学物质,具有广泛的应用.
- 目前的生产依赖于Aspergillus terreus,这是一个具有工业挑战的真菌病原体.
- 开发替代,安全的生产主机对于可扩展的伊塔康酸制造至关重要.
研究的目的:
- 为了设计一般公认的安全 (GRAS) 酵母Yarrowia lipolytica,以实现高效的伊塔康酸生产.
- 为了克服与阿斯伯吉勒斯土壤 (Aspergillus terreus) 相关的局限性,在伊塔科尼酸发酵中.
- 建立强大的发酵策略,用于工业规模的伊塔康酸合成.
主要方法:
- 雅罗维亚脂质菌的代谢工程,以重定向从脂质积累的碳流.
- 优化 itaconic 酸生物合成途径,包括细胞内和线粒体局部化.
- 通过使用遗传工具 (促进剂,RNAi,CRISPRi) 下调NAD+依赖的异酸脱酶来模拟限.
- 优化料批发发酵,用于高度生产.
主要成果:
- 工程化Yarrowia lipolytica以防止碳转移到脂质合成中.
- 取得的高伊塔克酸标位:在1L生物反应堆中达到130.1g/L,在50L半导体生物反应堆中达到94.8g/L.
- 证明了Yarrowia lipolytica的成功工业规模潜力,用于生产伊塔康酸.
结论:
- 雅罗维亚 (Yarrowia lipolytica) 可以有效地被设计成一种安全且具有竞争力的宿主,用于生产伊塔康酸.
- 开发的代谢工程和发酵策略为工业化伊塔康酸制造提供了可行的途径.
- 这项工作提供了一个有前途的替代品,以目前的伊塔康酸生产方法,利用一个GRAS微生物.
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