使用具有高效电子转移和改进的5-氨基氨酸合成的工程生物催化剂生产17α-基,并与P450氧酶结合
Jie Li1, Jikai Gao1, Jiaying Ai1
1Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, National Engineering Laboratory for Industrial Enzymes, Tianjin 300457, PR China.
International journal of biological macromolecules
|June 2, 2024
概括
研究人员开发了一种高效的方法,使用工程微生物生产17α-Hydroxyprogesterone (17α-OH-PROG). 这种优化的生物转化过程显著增加了产量,为制药应用提供了具有成本效益的解决方案.
科学领域:
- 生物技术是生物技术.
- 酶工程是什么? 酶工程是什么?
- 代谢工程是代谢工程.
背景情况:
- 17α-Hydroxyprogesterone (17α-OH-PROG) 是一个重要的制药中间体.
- 有效的生产方法对于其工业应用至关重要.
- 目前的方法在收益率和成本效益方面面临挑战.
研究的目的:
- 开发一种高效的全细胞生物催化剂,用于17α-OH-PROG生产.
- 优化生物转化条件以获得最大产量.
- 通过改造血红素生物合成途径来降低生产成本.
主要方法:
- 使用双等离子体系统对CYP260A1,Fpr和Adx的工程表达.
- 优化反应条件,并添加多素B.
- 引入一种修改后的C5通路,用于内源性血红素前体的合成.
主要成果:
- 通过关键酶的共同表达,实现了生物转化效率的提高.
- 在12小时内,优化条件和多素B的添加使17α-OH-PROG的产量从12.52 mg/L增加到102.37 mg/L.
- 综合修改的C5通路消除了对外部5-氨基氨酸 (ALA) 的需求,降低了工艺成本.
结论:
- 开发的全细胞生物催化剂代表了17α-OH-PROG生产的重大进步.
- 这一策略为P450酶的工业应用提供了一种有前途且具有成本效益的方法.
- 该研究强调了工程微生物系统在生产有价值的基化中间体方面的潜力.
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