Discovery, Biosynthetic Origin, and Heterologous Production of Massinidine, an Antiplasmodial Alkaloid

Bacteria of the genus Massilia represent an underexplored source of bioactive natural products. Here, we report the discovery of massinidine (1), a guanidine alkaloid with antiplasmodial activity, from these microbes. The unusual scaffold of massinidine is shown to originate from l-phenylalanine, acetate, and l-arginine. Massinidine biosynthesis genes were identified in the native producer and validated through heterologous expression in Myxococcus xanthus. Bioinformatic analyses indicate that the potential for massinidine biosynthesis is distributed in various proteobacteria.