Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines

作者：Wenxue Wang, Peng Wang, Chuanteng Ma, Shuo Li, Zian Wang, Yuting Liu, Lu Wang, Guojian Zhang, Qian Che, Tianjiao Zhu, Yu‐Zhong Zhang, Dehai Li · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-024-55537-8 · 被引用次数：8 · 研究领域：Microbial Natural Products and Biosynthesis、Plant biochemistry and biosynthesis、Plant Gene Expression Analysis

Prenylation modifications of natural products play essential roles in chemical diversity and bioactivities, but imidazole modification prenyltransferases are not well investigated. Here, we discover a dimethylallyl tryptophan synthase family prenyltransferase, AuraA, that catalyzes the rare dimethylallylation on the imidazole moiety in the biosynthesis of aurantiamine. Biochemical assays validate that AuraA could accept both cyclo-(L-Val-L-His) and cyclo-(L-Val-DH-His) as substrates, while the prenylation modes are completely different, yielding C2-regular and C5-reverse products, respectively. Cryo-electron microscopy analysis of AuraA and its two ternary complex structures reveal two distinct modes for receptor binding, demonstrating a tolerance for altered orientations of highly similar receptors. The mutation experiments further demonstrate the promiscuity of AuraA towards imidazole-C-dimethylallylation. In this work, we also characterize a case of AuraA mutant-catalyzed dimethylallylation of imidazole moiety, offering available structural insights into the utilization and engineering of dimethylallyl tryptophan synthase family prenyltransferases. Prenylation modifications of natural products play essential roles in chemical diversity and bioactivities, but imidazole modification prenyltransferases are not well investigated. Here, the authors discover and characterize a dimethylallyl tryptophan synthase family prenyltransferase, AuraA, that catalyzes the rare dimethylally...