中科院上海有机所的刘文课题组与美国加州大学洛杉矶分校的K. N. Houk课题组合作，阐明了一种Diels-Alder环加成酶PyrI4的催化机理。该项研究成果发表在2020年11月14日出版的《美国化学会志》上。

该团队研究了由单功能D-A酶PyrI4催化的分子内Diels–Alder反应的活化和立体选择性机理，天然产物吡咯菌素家族的生物合成中关键的螺环-四环骨架的形成即由该酶催化。PyrI4的关键活化效应主要来自酸催化、构象诱导适应机制以及与之配合的PyrI4的独特“加盖”特征以稳定D-A反应过渡态。

研究表明，PyrI4酶增强了底物内在的Diels-Alder立体选择性，导致产物的立体选择性合成。

附：英文原文

Title: Computational Investigation of the Mechanism of Diels–Alderase PyrI4

Author: Yike Zou, Song Yang, Jacob N. Sanders, Wei Li, Peiyuan Yu, Hongbo Wang, Zhijun Tang, Wen Liu, K. N. Houk

Issue&Volume: November 14, 2020

Abstract: We studied the mechanisms of activation and stereoselectivity of a monofunctional Diels–Alderase (PyrI4)-catalyzed intramolecular Diels–Alder reaction that leads to formation of the key spiro-tetramate moiety in the biosynthesis of the pyrroindomycin family of natural products. Key activation effects of PyrI4 include acid catalysis and an induced-fit mechanism that cooperate with the unique “lid” feature of PyrI4 to stabilize the Diels–Alder transition state. PyrI4 enhances the intrinsic Diels–Alder stereoselectivity of the substrate and leads to stereospecific formation of the product.

DOI: 10.1021/jacs.0c10813

Source: https://pubs.acs.org/doi/10.1021/jacs.0c10813