Wang Huibin, Yang Yi, Abe Ikuro
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Collaborative Research Institute for Innovative Microbiology, The University of Tokyo Yayoi 1-1-1, Bunkyo-ku, Tokyo, 113-8657, Japan.
Angew Chem Int Ed Engl. 2024 Dec 20;63(52):e202415279. doi: 10.1002/anie.202415279. Epub 2024 Nov 11.
In recent years, there has been a growing interest in understanding the enzymatic machinery responsible for the modifications of prenyl side chains and elucidating their roles in natural product biosynthesis. This interest stems from the pivotal role such modifications play in shaping the structural and functional diversity of natural products, as well as from their potential applications to synthetic biology and drug discovery. In addition to contributing to the diversity and complexity of natural products, unique modifications of prenyl side chains are represented by several novel biosynthetic mechanisms. Representative unique examples of epoxidation, dehydrogenation, oxidation of methyl groups to carboxyl groups, unusual C-C bond cleavage and oxidative cyclization are summarized and discussed. By revealing the intriguing chemistry and enzymology behind these transformations, this comprehensive and comparative review will guide future efforts in the discovery, characterization and application of modifications of prenyl side chains in natural product biosynthesis.
近年来，人们对了解负责异戊烯基侧链修饰的酶机制及其在天然产物生物合成中的作用越来越感兴趣。这种兴趣源于这些修饰在塑造天然产物的结构和功能多样性方面所起的关键作用，以及它们在合成生物学和药物发现中的潜在应用。除了促进天然产物的多样性和复杂性外，异戊烯基侧链的独特修饰还表现为几种新颖的生物合成机制。本文总结并讨论了环氧化、脱氢、甲基氧化为羧基、异常碳-碳键断裂和氧化环化等具有代表性的独特例子。通过揭示这些转化背后有趣的化学和酶学，这篇全面的比较综述将指导未来在天然产物生物合成中发现、表征和应用异戊烯基侧链修饰方面的工作。
