在Mycolicibacterium neoaurum中设计一个两种酶系统,以有效地将植物转化为二二
Zhenhua Su1, Chang Shi1, Yunshuang Fan1
1Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
International journal of biological macromolecules
|December 7, 2024
概括
工程微生物现在可以在单个步骤中从植物固醇中产生二二 (DHT). 这种可持续的生物转化为这种有价值的类固醇药物提供了比传统化学合成更绿色的替代方案.
科学领域:
- 生物技术是生物技术.
- 合成生物学 合成生物学
- 生物催化剂是一种生物催化剂.
背景情况:
- 二激素 (DHT) 是一种临床上重要的类固醇激素.
- 传统的DHT化学合成对环境来说是繁重和复杂的.
- 需要可持续和高效的DHT生产方法.
研究的目的:
- 开发一种单步微生物转化方法,从植物中产生DHT.
- 为了改造Mycolicibacterium neoaurum进行增强的DHT生物合成.
- 为了优化生物工艺的格拉姆尺度DHT产量.
主要方法:
- 工程化Mycolicibacterium neoaurum (MNR) 表达5α-减少酶 (5α-R) 和17β-基类固醇脱酶 (17β-HSD).
- 半理性突变发生来增强5α-R活性.
- 整合了一个基于PntAB的NADPH再生系统.
- 过程优化和分子动力学模拟.
主要成果:
- 使用工程MNR. 实现了植物醇转化为DHT的高效转化.
- 通过酶工程和系统优化,显著增强了DHT生产.
- 达到了1.123g·L-1的最大DHT度,标志着第一个克级微生物生产.
- 与化学合成相比,证明反应条件较温和,环境影响较小.
结论:
- 已经建立了一种可持续和高效的单步微生物方法,用于从植物醇中生产DHT.
- 这种生物转化过程为DHT的工业制造提供了一个更绿色的替代方案.
- 改造的MNR菌株和优化过程对类固醇激素药物生产具有重大潜力.
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