选择性酸化和二醇通过PsiK激酶及其变体
Ahram Kim1, Nicolás M Morato2, Prabir Saha1
1Department of Chemistry, Indiana University, Bloomington, Indiana, 47405, USA.
Angewandte Chemie (International ed. in English)
|June 17, 2025
概括
研究人员探索了PsiK,一种用于选择性酸化的酶. 他们扩大了其和二醇的基质范围,以高效率实现了格拉姆尺度合成.
科学领域:
- 生物化学 生化学
- 合成生物学 合成生物学
- 酶工程是什么? 酶工程是什么?
背景情况:
- 酸化是调节分子功能的关键生物过程.
- 生物催化酸化提供了使用ATP的选择性和温和反应条件.
- 激酶在小分子上活跃,具有显著的合成潜力.
研究的目的:
- 为了研究PsiK的基质范围,Psilocybe cubensis中的一种酶参与了psilocybin生物合成.
- 探索PsiK及其工程变异的潜力,用于各种化合物的准备性酸化.
- 为了证明DESI-MS在酶工程中的高通量选中的实用性.
主要方法:
- 使用PsiK与各种替代的和二醇进行酶活性测定.
- 位点定向突变发生,以设计PsiK的活性位点,以改变基质特异性.
- 溶解电喷电离化质谱仪 (DESI-MS) 用于快速反应选.
- 制剂规模的酸化反应和产品的表征.
主要成果:
- 比起其原生基质,PsiK对更广泛的替代和二醇表现出活性.
- 工程设计的PsiK变体表现出扩大了基质范围和改进了站点选择性.
- 通过DESI-MS查,在40分钟内快速分析了2688个反应.
- 实现了格拉姆尺度酸化,营业额超过10,000.
结论:
- PsiK是一种多功能生物催化剂,用于选择性酸化和二醇.
- 酶工程可以显著提高PsiK在合成应用中的实用性.
- 这项工作扩大了生物催化化工具包,提供了温和高效的合成途径.
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