A Rebeccamycin Analog Provides Plasmid-Encoded Niche Defense

Abstract

Bacterial symbionts of fungus-growing ants occupy a highly specialized ecological niche and face the constant existential threat of displacement by another strain of ant-adapted bacteria. As part of a systematic study of the small molecules underlying this fraternal competition, we discovered an analog of the antitumor agent rebeccamycin, a member of the increasingly important indolocarbazole family. While several gene clusters consistent with this molecule's newly reported modification had previously been identified in metagenomic studies, the metabolite itself has been cryptic. The biosynthetic gene cluster for 9-methoxyrebeccamycin is encoded on a plasmid in a manner reminiscent of plasmid-derived peptide antimicrobials that commonly mediate antagonism among closely related Gram-negative bacteria.

Figure 1

Intruder assay for ant-associated Pseudonocardia strains. The ability of the resident strain (center) to suppress growth of the intruder (periphery) is judged by the size of the zone of inhibition.

Figure 2

The genetic basis of BCI2 niche defense. (A) BCI2-specific plasmid encoding the biosynthetic gene cluster for 9-methoxyrebeccamycin. (B) The 9-methoxyrebeccamycin biosynthetic gene cluster and two related clusters. The conserved biosynthetic genes are named and color-coded.