在Komagataella phaffii中重新连接中央新陈代谢,以实现高效的曼诺合成
Sijia Zhao1,2, Yuheng Wang1, Qian Li2
1State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, No.2 Yuanmingyuan West Road, Haidian district, Beijing, 100193, China.
Microbial cell factories
|December 10, 2025
概括
康玛格塔拉 (Komagataella phaffii) 酵母的代谢工程使得高效的曼诺斯生产成为可能. 这项研究通过优化发酵策略,实现了121.1g/L曼诺的记录标位.
科学领域:
- 合成生物学 合成生物学
- 代谢工程是代谢工程.
- 微生物发酵过程中的微生物发酵.
背景情况:
- 通过微生物发酵生产曼诺斯是不发达的.
- 科马加泰拉法菲 (Komagataella phaffii) 是一种强大的酵母平台,用于高密度发酵.
- 代谢工程可以优化K. phaffii用于曼诺斯生物合成.
研究的目的:
- 为了设计K. phaffii以实现高效的曼诺斯生产.
- 建立一个双碳源系统,用于曼诺合成.
- 将新陈代谢流转向曼诺斯的积累.
主要方法:
- 通过基因淘汰和降低调节 (pfk2, pfk1, zwf1) 改造了K. phaffii.
- 抑制的曼诺酸异构酶和过度表达的大肠杆菌yniC,以增强曼诺酸的转化.
- 删除了参与阿拉比尼托和利比托生产的基因,以尽量减少副产品.
主要成果:
- 在高细胞密度料批发发酵中达到大约121.1g/L的曼诺斯.
- 通过微生物发酵证明了迄今为止报告的最高曼诺酸标位.
- 成功地将碳流转向果糖-6-酸盐和随后的曼诺合成.
结论:
- 在K. phaffii中通过中央代谢重塑实现了高效的曼诺斯生产.
- 呈现了微生物曼诺斯生物合成的新途径.
- 建立了一个工程 K. phaffii 其他生物活性化合物的框架.
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