Catalytic repertoire of bacterial bisindole formation

Bacterial bisindole alkaloids that derive from the oxidative dimerization of l-tryptophan possess diversified biological activities and unique molecular structures. In recent years, the number of bisindoles and their gene clusters has greatly expanded, revealing a large genetic toolbox for the generation of unique structural modifications. In this review, we will discuss the enzymatic pathways leading to diverse bisindoles structures. We will focus on the discovery of molecules through metagenomic mining, the elucidation of new enzymatic mechanisms, and the identification of new biosynthetic protecting group strategies. We will also highlight the newest work in combinatorial engineering and synthetic biology.