Characterization of an environmental DNA derived gene cluster that encodes for the bisindolylmaleimide methylarcyriarubin

摘要

Bisindolylmaleimides represent a naturally occurring class of metabolites that are of interest because of their protein kinase inhibition activity. From a metagenomic library constructed using soil DNA, we identified the four gene mar cluster, a bisindolylmaleimide gene cluster that encodes for methylarcyriarubin (>1) production. Heterologous expression of the mar gene cluster in Escherichia coli 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 mar cluster defines a new role for CPA in the biosynthesis of structurally diverse bacterial tryptophan dimers.