组合代谢工程用于改善Saccharomyces cerevisiae中的贝图林酸生物合成
Mei Tang1,2, Xianhao Xu1,2, Yanfeng Liu1,2
1Science Center for Future Foods, Jiangnan University, Wuxi 214122, China.
ACS synthetic biology
|May 15, 2024
概括
这项研究将酵母改造为生产贝鲁林酸 (BA),这是一种具有抗癌和抗HIV特性的化合物. 通过系统的代谢工程,研究人员在微生物细胞工厂中显著提高了BA生物合成效率.
科学领域:
- 生物技术是生物技术.
- 合成生物学 合成生物学
- 代谢工程是代谢工程.
背景情况:
- 贝图林酸 (BA) 是一种狼类型的三基,具有显著的抗癌和抗HIV活性.
- 有效的合成策略对于 betulinic 酸的临床应用至关重要.
- 微生物生产为传统提取方法提供了一个可持续的替代方案.
研究的目的:
- 在*Saccharomyces cerevisiae**中开发一种高效的贝鲁丁酸 (BA) 生物合成途径.
- 通过系统的代谢工程策略,优化BA生产.
- 建立一个强大的微生物细胞工厂用于化物生产.
主要方法:
- 在Saccharomyces cerevisiae*中构建一个 *de novo* BA生物合成途径.
- 增强BA合成途径和动态抑制竞争途径.
- 优化乙-CoA和NADPH的供应.
- 构建一个双氧体和细胞质BA合成途径.
- 料批发发酵过程的修改.
主要成果:
- 获得的初始BA标位为14.01 ± 0.21 mg/L.
- 改进导致标位为88.07±5.83毫克/升.
- 增加的前体供应将标位提高到166.43±1.83 mg/L.
- 双通道工程的结果是210.88 ± 4.76 mg / L.
- 最终优化料批发发酵达到682.29±8.16毫克/升的标位.
结论:
- 系统的代谢工程显著增强了Saccharomyces cerevisiae*中的贝鲁林酸 (BA) 生物合成.
- 优化前体供应和双路调节是高产量生产的关键.
- 这项工作为开发用于化物生产的微生物细胞工厂提供了有价值的框架.
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