系统代谢工程用于改善Candida tropicalis中酸的合成
Haiquan Yang1, Jinrong Guo2, Lihua Zhang3
1The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, China.
Applied microbiology and biotechnology
|August 27, 2024
概括
工程酵母Candida tropicalis现在通过新合成产生酸,一种潜在的抗癌药物. 这一突破在5L发酵器中实现了106.69mg/L的标位,为微生物生产有价值的化学物质铺平了道路.
科学领域:
- 代谢工程是代谢工程.
- 合成生物学 合成生物学
- 微生物生物技术 微生物生物技术
背景情况:
- 酸作为抗癌和抗微生物药物表现有前途,引发了对其高效生产的兴趣.
- 热带菌 (Candida tropicalis) 是一种能够代谢和脂肪酸的酵母,为生物生产提供了一个独特的平台.
- 之前在酸合成中的局限性需要开发新的微生物生产策略.
研究的目的:
- 为了设计Candida tropicalis用于新合成酸.
- 为了优化L-limonene的生产,这是酸的关键前体,在工程C. tropicalis.中.
- 建立微生物发酵过程,以达到显著的酸标位.
主要方法:
- 在C. tropicalis中,Mentha spicata的L-烯合成酶基因 (LS_Ms) 的异质表达产生L-烯.
- 通过前体合成基因和突变ERG20WW基因的细胞质过度表达来优化L-烯的产生.
- 萨尔维亚多菌细胞染色体P450酶基因 (CYP7176) 和Arabidopsis thaliana NADPH细胞染色体P450减少酶基因 (CPR) 的联合表达用于酸合成.
主要成果:
- 工程C. tropicalis通过前体基因的细胞质过度表达实现了L-烯产量的31.7倍增加.
- 随着突变ERG20WW基因的细胞质过度表达,观察到L-烯标位进一步增大11.33倍.
- 在工程化C. tropicalis中成功地新合成了酸,在5L发酵器中达到106.69mg/L的标位.
结论:
- 关键基因的细胞质表达对于增强C. tropicalis. 中的L-烯生产至关重要.
- 这项研究报告了首次在工程微生物中成功合成酸的新合成.
- 工程设计的C. tropicalis平台显示了微生物高效生产酸和其他有价值的化学物质的潜力.
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