Download MendeleyDiscovery, Characterization and Engineering of the Free l-Histidine C4 -Prenyltransferase.
Chen, X.W., Liu, Z., Dai, S., Zou, Y.(2024) J Am Chem Soc 146: 23686-23691
- PubMed: 39140691
- DOI: https://doi.org/10.1021/jacs.4c08388
- Primary Citation of Related Structures:
9IIA - PubMed Abstract:
Prenylation of amino acids is a critical step for synthesizing building blocks of prenylated alkaloid family natural products, where the corresponding prenyltransferase that catalyzes prenylation on free l-histidine (l-His) has not yet been identified. Here, we first discovered and characterized a prenyltransferase FunA from the antifungal agent fungerin pathway that efficiently performs C4 -dimethylallylation on l-His. Crystal structure-guided engineering of the prenyl-binding pocket of FunA, a single M181A mutation, successfully converted it into a C4 -geranyltransferase. Furthermore, FunA and its variant FunA-M181A show broad substrate promiscuity toward substrates that vary in substituents of the imidazole ring. Our work furthers our knowledge of free amino acid prenyltransferase and expands the arsenal of alkylation biocatalysts for imidazole-containing small molecules.
Organizational Affiliation:
College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, P. R. China.
