工程 Pichia pastoris 对于高价值的类固醇中间体15α-OH-D-乙基宁的高效生产
Yu-Long Zeng1,2,3, Yang-Yang Li4,2,3, Bei-Feng-Chu Zheng4,2,3
1College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310032, Zhejiang, China.
Microbial cell factories
|July 20, 2025
概括
工程酵母产生15α-OH-DE,这是类固醇药物gestodene的关键中间体,达到创纪录的标位. 这种可持续的生物转化为制药生产提供了有效的替代方案.
科学领域:
- 生物技术是生物技术.
- 合成生物学 合成生物学
- 微生物工程 微生物工程
背景情况:
- 15α-OH-D-乙烯基 (15α-OH-DE) 对于合成现代避孕药的成分gestodene至关重要.
- 15α-OH-DE的化学合成效率低下,产生低位和有毒的副产品.
研究的目的:
- 为15α-OH-DE生产开发一种可持续和高效的生物工艺.
- 设计Pichia pastoris作为一种用于类固醇生物转化的全细胞催化剂.
主要方法:
- 在Pichia pastoris中,Penicillium raistrickii PRH基因 (类固醇15α-基酶) 和面包酵母ZWF1基因 (对NADPH) 的联合过度表达.
- 在摇瓶培养中优化发酵参数.
- 扩大生物转化过程的规模,使用5L生物反应器中的料批发发酵和甲醇诱导.
主要成果:
- 工程Pichia pastoris实现了创纪录的15α-OH-DE标位5.79g L-1.1,一个L-1.1.
- 该过程使用纯甲醇作为碳源和诱导剂.
- 成功的扩展证明了工程系统的可行性.
结论:
- 皮奇亚牧草是开发高效生物转化系统的有希望的宿主.
- 这种工程菌株为生产类固醇制药中间体提供了一条可持续的途径.
- 获得的高标位代表了微生物生产精细化学品的重大进步.
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