On November 20, the team led by Prof. Zhu Weiming from the School of Medicine and Pharmacy, in collaboration with Prof. Li Shengying’s team from Shandong University, published their latest research progress in the Journal of the American Chemical Society. The paper titled “Biosynthesis of 4-Acyl-5-aminoimidazole Alkaloids Featuring a New Friedel–Crafts Acyltransferase” highlights significant advancements in the field.

The formation of carbon-carbon bonds is a key step in constructing the structure of organic compounds. The Friedel-Crafts acylation is a significant reaction in this context, facilitating the formation of carbon-carbon bonds between aromatic substrates and acyl groups. This reaction produces a diverse range of aromatic ketone structures, widely applied in the pharmaceutical industry. 

Researchers initially identified the AAIAs biosynthetic gene cluster (smz) in Streptomyces sp. OUCMDZ-944 through large-scale gene knockout and heterologous expression experiments. Subsequent single-gene deletion mutation experiments further clarified the four key genes essential for the synthesis of the alkaloid structure: smzB, -C, -E, and -F. By combining the functional predictions of these key genes with the changes in the metabolic profiles of the mutant strains, they gradually unraveled the mystery of the novel FCase SmzB. 

This article, based on the discovery of seven new 4-acyl-5-aminoimidazole alkaloids (AAIAs) natural products, elucidates for the first time the biosynthetic pathway of AAIAs. It reveals the interplay and interaction between two primary metabolisms—purine metabolism and fatty acid metabolism—in the formation of AAIAs. Through this research, a unique and novel FCase-SmzB, was discovered.