Download MendeleyCharacterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines.
Wang, W., Wang, P., Ma, C., Li, K., Wang, Z., Liu, Y., Wang, L., Zhang, G., Che, Q., Zhu, T., Zhang, Y., Li, D.(2025) Nat Commun 16: 144-144
- PubMed: 39747040
- DOI: https://doi.org/10.1038/s41467-024-55537-8
- Primary Citation of Related Structures:
8Y9D, 8Y9E, 8Y9G, 9JHX - PubMed Abstract:
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.
Organizational Affiliation:
Key Laboratory of Marine Drugs Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, P R China.
