The recent identification of genes encoding a novel family of soluble aromatic prenyltransferases from Streptomyces species and the structural characterization of one of these proteins are challenging discoveries in the biochemistry of natural compounds. In addition to their notable physiological role in the biosynthesis of aminocoumarin antibiotics, these enzymes represent an advanced tool for exploring novel isoprenoid substitutions in aromatic compounds and are expected to foster the emerging pharmacological applications of prenylated flavonoids.