美国加州大学Yang, Yang团队报道了催化不对称自由基脱芳的金属酶平台。相关研究成果发表在2024年8月28日出版的《自然—化学》。

催化不对称脱芳烃是一种将扁平芳香族化合物，转化为立体化学上定义良好的三维分子支架的有力手段。

利用新的自然金属氧化还原生物催化，研究人员描述了一种小分子催化剂所无法实现的，通过具有挑战性的自由基机制实现的酶催化不对称脱芳烃的策略。

通过定向转化，新的天然自由基脱芳烃酶P450rad1-P450rad5促进了包括吲哚、吡咯和酚在内的广谱芳香底物的不对称脱芳烃，使对映体转化剂和对映体碘向自由基脱芳反应都能在良好的酶控制下完成。

计算研究揭示了工程金属酶和反应性中间体之间额外氢键相互作用，在增强酶活性和对映体控制方面的重要性。此外，研究发现，设计的非离子表面活性剂可以显著加速这种生物转化，为促进原本缓慢的新自然生物转化提供了一种替代方法。

总之，该可进化的金属酶平台为推进涉及自由基中间体的，具有挑战性的催化不对称脱芳烃过程开辟了新的途径。

附：英文原文

Title: A metalloenzyme platform for catalytic asymmetric radical dearomatization

Author: Fu, Wenzhen, Fu, Yue, Zhao, Yunlong, Wang, Huanan, Liu, Peng, Yang, Yang

Issue&Volume: 2024-08-28

Abstract: Catalytic asymmetric dearomatization represents a powerful means to convert flat aromatic compounds into stereochemically well-defined three-dimensional molecular scaffolds. Using new-to-nature metalloredox biocatalysis, we describe an enzymatic strategy for catalytic asymmetric dearomatization via a challenging radical mechanism that has eluded small-molecule catalysts. Enabled by directed evolution, new-to-nature radical dearomatases P450rad1–P450rad5 facilitated asymmetric dearomatization of a broad spectrum of aromatic substrates, including indoles, pyrroles and phenols, allowing both enantioconvergent and enantiodivergent radical dearomatization reactions to be accomplished with excellent enzymatic control. Computational studies revealed the importance of additional hydrogen bonding interactions between the engineered metalloenzyme and the reactive intermediate in enhancing enzymatic activity and enantiocontrol. Furthermore, designer non-ionic surfactants were found to significantly accelerate this biotransformation, providing an alternative means to promote otherwise sluggish new-to-nature biotransformations. Together, this evolvable metalloenzyme platform opens up new avenues to advance challenging catalytic asymmetric dearomatization processes involving free radical intermediates.

DOI: 10.1038/s41557-024-01608-8

Source: https://www.nature.com/articles/s41557-024-01608-8