转录学驱动的 Yarrowia lipolytica 工程用于增强脂肪酸生物合成
He Qiao1,2, Zaihang Dong1,2, Bofan Yu1,2
1College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China.
ACS synthetic biology
|August 15, 2025
概括
我们开发了Findgene,这是一个计算管道,用于发现Yarrowia lipolytica中的调节基因. 这种工具提高了脂肪酸生产的2.9倍,优化了微生物细胞工厂的生物制造.
科学领域:
- 微生物生物技术 微生物生物技术
- 系统生物学 系统生物学
- 代谢工程是代谢工程.
背景情况:
- 亚罗维亚脂质菌 (Yarrowia lipolytica) 是生物制造的关键微生物底盘.
- 有限的遗传注释和调控元素的表征阻碍了有效的菌株发展.
- 庞大的转录基因数据对于系统的基因发现仍未得到充分利用.
研究的目的:
- 开发一个计算管道 (Findgene) 以在Y. lipolytica.中有效地发现调节基因.
- 确定参与脂肪酸代谢的新型调节基因.
- 为了改造Y. lipolytica以提高脂肪酸的生产.
主要方法:
- 综合标准化转录基因元分析与权重基因共表达网络分析 (WGCNA).
- 将Findgene管道应用于Y. lipolytica的转录数据.
- 进行候选基因的实验验证,包括基因替代和过度表达.
主要成果:
- 确定了六个与脂肪酸代谢相关的候选调节基因.
- 将YALI0B12342g替换为G643R突变体增加了131%的总脂肪酸产量.
- 过度表达YALI0A07733g和YALI0A20207g显著增加脂肪酸标位.
- 一个组合策略实现了总脂肪酸产量的2.9倍增长.
结论:
- 寻找基因管道使调节基因的有效和经济的发现成为可能.
- 工程化Y. lipolytica菌株显示出大量生产脂肪酸衍生化合物的巨大潜力.
- Findgene框架可适应其他非传统酵母物种的工程设计.
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