Biosynthesis of Indolocarbazoles in a Heterologous E. coli Host

The antitumor antibiotic rebeccamycin (1), produced by the bacterium Saccharothrix aerocolonigenes, is a prototype of a class of complex natural products called indolocarbazoles. The cloning and characterization of the rebeccamcyin (reb) gene locus from S. aerocolonigenes is reported. The heterologous expression of this intact gene cluster in Escherichia coli led to the production of 1 and two putative biosynthetic intermediates. This work represents the first production of indolocarbazole analogues in the heterologous host E. coli.