<jats:title>Abstract</jats:title><jats:p>Bisindolylmaleimides represent a naturally occurring class of metabolites that are of interest because of their protein kinase inhibition activity. From a metagenomic library constructed with soil DNA, we identified the four gene <jats:italic>mar</jats:italic> cluster, a bisindolylmaleimide gene cluster that encodes for methylarcyriarubin (<jats:bold>1</jats:bold>) production. Heterologous expression of the <jats:italic>mar</jats:italic> gene cluster in <jats:italic>E. coli</jats:italic> revealed that the Rieske dioxygenase MarC facilitates the oxidative decarboxylation of a chromopyrrolic acid (CPA) intermediate to yield the bisindolylmaleimide core. The characterization of the <jats:italic>mar</jats:italic> cluster defines a new role for CPA in the biosynthesis of structurally diverse bacterial tryptophan dimers.