在Yarrowia lipolytica中最大限度地提高三烯生产的工程氧体生物合成途径
Yongshuo Ma1, Yi Shang2,3, Gregory Stephanopoulos1
1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142.
概括
在Yarrowia lipolytica中,工程化过氧体有效地通过隔离其合成来产生素. 这一策略显著提高了烯产量,提供了一种生产乙-CoA衍生代谢物的新方法.
科学领域:
- 代谢工程是代谢工程.
- 合成生物学 合成生物学
- 生物技术是生物技术.
背景情况:
- 细胞工厂的效率受到竞争的代谢途径和前体可用性的限制.
- 在Yarrowia lipolytica中,烯生物合成与必要的固醇生产有关,从而产生竞争.
研究的目的:
- 为了改造Yarrowia lipolytica以提高烯的产量.
- 克服前体供应的局限性和三二生物合成的竞争途径.
主要方法:
- 在过氧体内重建了烯生物合成途径.
- 通过脂质转化和CO2衍生的酸盐,增强过氧体乙-CoA的供应.
- 利用生物反应器发酵来实现高产量生产.
主要成果:
- 与原生细胞质合成相比,斯卡伦水平增加了1300倍.
- 工程菌株从葡萄糖中产生了32.8g/L的斯夸伦,从乙酸产生了31.6g/L的斯夸伦.
- 在Peroxisomes中证明了烯合成的有效封存.
结论:
- 在Y. lipolytica中,Peroxisome工程作为乙-CoA衍生代谢物的微工厂.
- 这一策略保护中间体免受竞争反应的影响,使高产量生产成为可能.
- 提供了一种可行的方法来生产像烯这样有价值的化合物.
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