Fungal aromatic prenyltransferases: Characterization and product profiling

Antimicrobial resistance is increasing the need for new antimicrobial compounds. Inspired by natural defense systems, we focused on prenylated aromatic compounds, a large group of bioactive molecules from plants and microbes that often show strong antimicrobial activity. However, their exploration as lead compounds is limited due to their low abundance in nature, which complicates their isolation from biological sources. In this work, we explored a biotechnological strategy to produce and diversify aromatic molecules using fungal aromatic prenyltransferases (aPTs), enzymes that attach prenyl groups to aromatic compounds. Two novel aPTs were shown to prenylate a wide range of pharmaceutically relevant molecules, including aromatic amino acids and their (halogenated) derivatives, as well as plant phenolics. These aPTs preferentially attach the prenyl group to oxygen atoms, a modification that occurs less frequently in nature. Thereby, we expanded the diversity of available molecules for further research, and support the development of sustainable, enzyme-based methods to produce antimicrobial and other bioactive compounds.