对酶库的探究揭示了自然演化的 [4+2] 循环酶的催化可塑性
Katja Zorn1, Catherine R Back2, Rob Barringer2
1Compound Synthesis and Management, Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Pepparedsleden 1, 431 83, Mölndal, Sweden.
Chembiochem : a European journal of chemical biology
|June 12, 2023
概括
研究人员探索了Diels-Alder反应的酶,发现了可持续合成的新生物催化剂. 假设的蛋白质Cyc15独特地形成了一种新型的螺旋酸盐,揭示了其立体选择机制.
科学领域:
- 有机化学 有机化学
- 生物催化剂是一种生物催化剂.
- 酶学 是一种酶学.
背景情况:
- 立体选择性碳-碳键的形成在有机合成中至关重要.
- 迪尔斯-阿尔德反应,一个 [4+2] 循环加法,对于创建循环烯结构至关重要.
- 生物催化剂为这些必要的化学转化提供了可持续的途径.
研究的目的:
- 为了理解自然进化的 [4+2] 循环.
- 为了确定用于迪尔斯-阿尔德反应的新生物催化剂.
- 研究这些酶中的立体选择性机制.
主要方法:
- 45个酶库的构建和表达,预测有 [4+2] 循环添加活性.
- 在体外测试中使用具有二烯和二烯基成分的合成基质.
- 确定Cyc15酶的晶体结构的确定和计算对接研究.
主要成果:
- 45种酶中有31种已成功生产和测试.
- 在测试的酶库中观察到广泛的循环添加活性.
- 假设的蛋白质Cyc15催化了分子内循环添加,形成了一种新型的螺旋酸盐.
结论:
- 该研究确定了Diels-Alder反应的新生物催化剂,推动了可持续合成.
- 酶Cyc15表现出独特的活性,形成了一种新型的螺旋酸盐.
- 结构和对接分析阐明了Cyc15的立体选择机制,提供了与其他螺旋氨酸环酸相比的见解.
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