瑞士保罗谢勒研究所Li, Xiaodan团队报道了氧化苯乙烯异构酶催化Meinwald重排的结构基础。相关研究成果于2024年5月14日发表在《自然—化学》。

膜结合氧化苯乙烯异构酶（SOI）催化Meinwald重排——一种路易斯酸催化的环氧化物异构化为羰基化合物——并已用于单级和级联反应。然而，解释其反应机制的结构信息仍然难以捉摸。

该文中，研究人员确定了在有和没有竞争性抑制剂苄胺的情况下，与单结构域抗体结合的SOI的冷冻电子显微镜（cryo-EM）结构，并使用电子顺磁共振波谱、功能测定、生物物理方法和对接实验阐明了催化机制。研究发现铁血红素b通过H58结合在三聚酶的亚基界面，其中Fe（III）通过与环氧化物氧结合而作为路易斯酸。

Y103和N64以及分别结合环氧化物和芳基的氧的疏水袋，以解释SOI的高区域选择性和立体特异性的方式定位底物。该发现可以支持扩大环氧化物底物的范围，并可用于潜在地将SOI重新用于催化新的天然铁基化学反应。

附：英文原文

Title: Structural basis of the Meinwald rearrangement catalysed by styrene oxide isomerase

Author: Khanppnavar, Basavraj, Choo, Joel P. S., Hagedoorn, Peter-Leon, Smolentsev, Grigory, tefani, Saa, Kumaran, Selvapravin, Tischler, Dirk, Winkler, Fritz K., Korkhov, Volodymyr M., Li, Zhi, Kammerer, Richard A., Li, Xiaodan

Issue&Volume: 2024-05-14

Abstract: Membrane-bound styrene oxide isomerase (SOI) catalyses the Meinwald rearrangement—a Lewis-acid-catalysed isomerization of an epoxide to a carbonyl compound—and has been used in single and cascade reactions. However, the structural information that explains its reaction mechanism has remained elusive. Here we determine cryo-electron microscopy (cryo-EM) structures of SOI bound to a single-domain antibody with and without the competitive inhibitor benzylamine, and elucidate the catalytic mechanism using electron paramagnetic resonance spectroscopy, functional assays, biophysical methods and docking experiments. We find ferric haem b bound at the subunit interface of the trimeric enzyme through H58, where Fe(III) acts as the Lewis acid by binding to the epoxide oxygen. Y103 and N64 and a hydrophobic pocket binding the oxygen of the epoxide and the aryl group, respectively, position substrates in a manner that explains the high regio-selectivity and stereo-specificity of SOI. Our findings can support extending the range of epoxide substrates and be used to potentially repurpose SOI for the catalysis of new-to-nature Fe-based chemical reactions.

DOI: 10.1038/s41557-024-01523-y

Source: https://www.nature.com/articles/s41557-024-01523-y