皮质类固醇衍生物的生物催化合成由衍生的类固醇C21-氧酶
Meiling Duan1, Xueqing Zhong1, Jiaxu Qin1
1State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
这项研究优化了类固醇21-基酶 (CsCYP21A) 以增强C21-基化,使多种类固醇基质的有效生物转化成为有价值的制药前体.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 生物技术是生物技术.
背景情况:
- 类固醇21-氧化是类固醇激素生物合成和制药生产的关键步骤.
- 现有的类固醇修饰方法可能是低效的或环境负担.
- 来自 *Bufo bufo gargarizans* 的青酶 CsCYP21A 显示出具有新型氧化能力的潜力.
研究的目的:
- 为了优化Pichia pastoris*中CsCYP21A的生物转化条件.
- 评估CsCYP21A对C21-基化的基质范围和效率.
- 评估CsCYP21A作为绿色制药制造中的生物催化剂的潜力.
主要方法:
- 在Pichia pastoris*中,酶工程和CsCYP21A的异质表达.
- 优化发酵和生物转化参数.
- 使用分析技术分析基质转换和产品产量.
主要成果:
- 优化条件显著提高了C21-基化选择性和效率.
- CsCYP21A成功转化了14种不同的类固醇基质,10种转化率高于80%,4种产量高于80%.
- 在100g/L湿生物量下,实现了1.5gL-1天的高皮生产率.
结论:
- CsCYP21A在类固醇C21-基化中表现出了显著的多功能性和效率.
- 优化的生物催化系统为合成类固醇药物提供了一个可持续和绿色的平台.
- 这种酶有可能简化10多种类型的类固醇药物的生产.
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