不对称R-/S-PAC合成与以弗得林或伪以弗得林脱酶在皮克林乳液中的反应工程
Reynaldo Jr Carubio1, Bao-Hsiang Wang1, Marion B Ansorge-Schumacher1
1Chair of Molecular Biotechnology Dresden University of Technology Dresden Germany.
Engineering in life sciences
|February 24, 2025
概括
新型酶乙脱酶 (EDH) 和伪乙脱酶 (PseDH) 在生物活性皮克林乳液 (BioPE) 中用于合成酸. 这种方法实现了大规模制药生产的高时空收益率和转换.
科学领域:
- 生物催化和酶工程 生物催化和酶工程
- 绿色化学和可持续合成
- 纳米技术在化学过程中的应用
背景情况:
- 乙烯基酸酸,如乙烯基碳醇 (PAC),是重要的制药中间体.
- 新型酶乙脱酶 (EDH) 和伪乙脱酶 (PseDH) 为R-PAC和S-PAC提供了特定的路径.
- 皮克林乳液为可扩展的生物转化提供了一个有希望的反应介质.
研究的目的:
- 将EDH和PseDH集成到一个生物活性皮克林乳液 (BioPE) 系统中,以合成纯PAC.
- 使用实验设计 (DOE) 系统设计复杂的BioPE反应环境.
- 为了优化反应条件,最大限度地提高时空产量 (STY) 和转换.
主要方法:
- 开发一种由纳米颗粒稳定的油中的水皮克林乳液,使用甲基三-丁以太作为连续相.
- 在BioPE中对EDH和PseDH进行固定,以减少1-phenyl-1,2-propanedione (PPD).
- 实验设计 (DOE) 的应用,包括最终选设计和响应表面方法,以优化过程.
- 使用来自Rhodococcus jostii的形式脱酶的辅因子再生.
主要成果:
- 使用EDH的BioPE系统实现了4.2g L-1h-1的时空收益率 (STY) 和83.2%的转换率.
- 使用PseDH的BioPE系统显示STY为4.4gL-1h-1和64.5%的转化.
- 能源部成功确定了复杂的BioPE反应系统的关键因素和优化条件.
结论:
- 开发的生物活性皮克林乳液系统提供了一个高效和可扩展的平台,用于酶合成的enantiopurePAC.
- 使用DOE进行系统优化对于工程复杂的多相生物催化系统是有效的.
- 这种方法对工业生产合性制药中间体具有重大潜力.
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