Transformation-Guided Genome Mining Provides Access to Brominated Lanthipeptides.

Natural product biosynthesis is nature's tinkering ground for developing new enzymes that can achieve chemical transformations that are outside the purview of traditional chemical catalysis. Herein we describe a genome mining approach that leads to the discovery of a halogenase that regioselectively brominates a tryptophan side chain indole for a macrocyclic peptide substrate, enabling downstream chemical arylation by Suzuki-Miyaura coupling. The halogenase was found to prefer a macrocyclic peptide substrate over a linear peptide. The brominase presents a starting point for biocatalytic access to macrocyclic peptides bearing a chemically versatile aryl-bromide reactive handle.