Divergent Pathways in the Biosynthesis of Bisindole Natural Products

Two molecules of the amino acid L-tryptophan are the biosynthetic precursors to a class of natural products named the “bisindoles.” Hundreds of these bisindole molecules have been isolated from natural sources, and many of these molecules have potent medicinal properties. Recent studies have clarified the biosynthetic construction of six bisindole molecules, revealing novel enzymatic mechanisms and leading to combinatorial synthesis of new bisindole compounds. Collectively, these results provide a vantage point for understanding how much of the diversity of the bisindole class is generated from a small number of diverging pathways from L-tryptophan, as well as enabling identification of bisindoles that are likely derived via completely distinct biosynthetic pathways.Howard Hughes Predoctoral FellowshipNational Institutes of Health (U.S.) (grant GM65337