通过理性工程和发酵改进来增强Saccharopolyspora erythraea中的红色素生产:一个设计-构建-测试-学习的方法
Minghao Shao1, Feng Xu1, Xiang Ke1
1State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, People's Republic of China.
Biotechnology journal
|May 26, 2024
概括
使用设计-构建-测试-学习 (DBTL) 框架的代谢工程增强了Saccharopolyspora erythraea中的红色素生产. 优化发酵条件提高了43.5%的产量,为抗生素制造提供了新的战略.
科学领域:
- 微生物学 微生物学
- 代谢工程是代谢工程.
- 生物技术是生物技术.
背景情况:
- 像红红素这样的生物活性化合物的工业生产面临着巨大的挑战.
- 动氨菌是抗生素的关键来源,但优化其生产是复杂的.
- 代谢工程提供了一条改善抗生素生物合成效率的途径.
研究的目的:
- 通过使用设计-构建-测试-学习 (DBTL) 框架,增强Saccharopolyspora erythraea中的红色素生产.
- 为改进红红素合成,设计一种具有抑制 sucC 基因的改性菌株 (S. erythraea CS).
- 调查增强抗生素生产背后的代谢变化.
主要方法:
- 设计-构建-测试-学习 (DBTL) 框架用于系统的代谢工程的应用.
- 通过使用dcas9和可诱导促进剂抑制succ基因,对Saccharopolyspora erythraea E3进行遗传修饰.
- 转录组和代谢组分析以了解细胞代谢变化.
- 通过硫酸补充剂优化发酵.
主要成果:
- 改造的S. erythraea CS菌株显示,由于前体可用性增加和NADPH增加,红红素合成得到改善.
- 代谢分析显示了中央碳,氨基酸,能量和辅助因子代谢的显著变化.
- 在发酵过程中补充硫酸导致红红素产量增加了43.5% (1125.66毫克L-1).
结论:
- 在S. erythraea. 中,DBTL方法有效优化红色素的产量.
- 代谢工程策略可以显著提高抗生素产量,解决制造业的挑战.
- 这种方法有望推动抗生素制造以打击抗菌素耐药性.
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