从葡萄糖中通过工程酵母细胞工厂从葡萄糖中生产复杂的类甘的高水平可持续生产
Penggang Bai1, Yihan Yang1, Jun Tang2
1University of Chinese Academy of Sciences, Beijing, 100049, China; Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China; National Center of Technology Innovation for Synthetic Biology, Tianjin, China; Key Laboratory of Engineering Biology for Low-carbon Manufacturing, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
Metabolic engineering
|November 27, 2024
概括
工程酵母成功地从葡萄糖中制造出复杂的乙基化物 (PhG),如Verbascoside和Echinacoside. 这种微生物生产为这些有价值的化合物提供了传统植物提取的可持续替代方案.
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:
- 复杂的乙基化物 (PhG),包括化物和化物,是有价值的营养药和制药化合物.
- 传统的植物提取方法产生的PhGs数量不足,需要使用替代的生产策略.
- 细菌菌 (酵母菌) 为微生物生产复杂的天然产品提供了一个有前途的平台.
研究的目的:
- 从葡萄糖中设计Saccharomyces cerevisiae细胞工厂,以高效地生产复杂的类糖化物 (PhG).
- 建立一个可持续和可扩展的微生物生产平台,用于verbascoside和echinacoside.
主要方法:
- 选的关键通路酶与增强的催化活动从植物生产的verbascoside.
- 通过过度表达特定的酶 (例如,RRUGT33,SiAT,SiRT,AtRHM2,At4CL1,PcAAS) 和操纵基因拷贝数量来对S. cerevisiae进行代谢工程.
- 生物合成基因 (CYP98A20,AtCPR1) 的整合和葡萄糖-6-酸盐脱酶 (ZWF1) 的过度表达用于途径优化.
- 在5L生物反应器中进行料批发发酵,用于大规模生产.
主要成果:
- 工程酵母从葡萄糖中产生了320.6±59.3毫克/升的中间奥斯曼化B.
- 维巴科赛德的产量达到了230.6±11.8 mg/L,而科赛德的产量达到了184.2±11.2 mg/L.
- 大规模的食批次发酵产生了高位数: 4497.9 ± 285.2 毫克/升的维巴斯科赛德和 3617.4 ± 117.4 毫克/升的乙科赛德.
结论:
- 成功设计了Saccharomyces cerevisiae作为一个细胞工厂,以高效地生产复杂的PhG.
- 展示了一个可持续和可扩展的微生物平台,用于工业生产的verbascoside和echinacoside.
- 为微生物生产其他复杂的类甘氨酸衍生物提供了基础.
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