使用非自然的蛋白质融合来设计酵母和哺乳动物细胞中的复星生物合成
Yansheng Zhang1, Song-Zhe Li, Jia Li
1Donald Danforth Plant Science Center, St. Louis, Missouri 63132, USA.
Journal of the American Chemical Society
|October 5, 2006
概括
研究人员设计了一种植物.
科学领域:
- 生物化学 生物化学
- 合成生物学 合成生物学
- 代谢工程是代谢工程.
背景情况:
- 植物衍生化合物白醇 (Resveratrol) 提供健康益处和延长寿命的特性.
- Resveratrol的生物合成涉及特定的酶,如铁氨酶 (TAL),4-酸盐CoA-酶 (4CL) 和斯蒂尔合成酶 (STS).
研究的目的:
- 在非植物宿主中建立一个新的复星生物合成途径.
- 调查酶局部化在增强复星生产中的效率.
主要方法:
- 来自不同生物体的编码TAL,4CL和STS的分离基因.
- 工程酵母和人类HEK293细胞用于产生复星.
- 利用转化融合蛋白来增强酶的近距离和途径的效率.
主要成果:
- 表达4CL和STS的酵母细胞从4-酸中产生复星.
- 4CL和STS的转化融合使酵母酵母中的白醇产量增加了15倍.
- 在人类HEK293细胞中成功实现了de novo复星生物合成和细胞内积累.
结论:
- 在哺乳动物宿主中设计了一个完整的植物天然产品通路.
- 证明了酶的物理局部化可以提高代谢途径的效率.
- 在哺乳动物细胞工厂中开辟了产生白醇的可能性.
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