构建一个全球模块化重组的Saccharomyces cerevisiae底盘,用于生产金科利德前体levopimaradiene
De Liu1, Ziqing Chen2, Zizheng Guo1
1Biotechnological Institute of Chinese Materia Medica, Jinan University, Guangzhou, 511443, China.
Synthetic and systems biotechnology
|February 16, 2026
概括
这项研究设计了Saccharomyces cerevisiae以产生levopimaradiene (LP),这是一个金金戈利德前体. 优化的代谢途径显著提高了LP的生产,实现了可持续天然产品制造的创纪录.
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:
- 使用Saccharomyces cerevisiae的微生物生产为天然产品提供了可持续的途径.
- 代谢工程的挑战包括菌株生长停滞和不稳定的流量.
- 莱沃皮马拉迪因 (LP) 是金金戈利德生物合成的关键前体.
研究的目的:
- 开发一种用于高效生产levopimaradiene (LP) 的重组Saccharomyces cerevisiae底盘菌株.
- 为了克服阻碍人工酵母合成天然产品的代谢瓶.
- 建立通过酵母发酵生产二烯的框架.
主要方法:
- 对levopimaradiene合成酶 (LPS) 的系统性修改.
- 调节美瓦酸路径.
- 增加乙-CoA,ATP和NADPH的供应.
- 优化发酵条件 (摇瓶和料批).
主要成果:
- 在摇瓶发酵中达到792.72 ± 69.59 mg/L的LP标位.
- 在料批发发酵中达到显著更高的LP标位1809.32 ± 72.32 mg/L.
- 与以前的菌株相比,LP标位增加了8.3倍,创造了新的纪录.
结论:
- 成功设计了Saccharomyces cerevisiae,用于高水平的levopimaradiene生产.
- 开发的战略为金金戈利德底盘工厂提供了一个强大的平台.
- 提供了适用于使用酵母生产其他二烯的概念框架.
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