The highly successful multilateral symbiosis featuring fungus-growing ants, their fungal crop, specialized pathogenic fungi (Escopvopsis spp.), chemical defense-producing bacteria (Pseudonocardia spp.) and other microbes has been a productive system both for the discovery of secondary metabolites and as an evolutionary model. The system had a single origin some 50-60 million years ago in the Amazon and has spread to over 200 species throughout Central and South America and southern states of the USA. This talk focuses on the biologically active small molecules produced by the Pseudonocardia spp. in our initial survey. These bacterial symbionts displayed remarkable molecular diversity at both the strain and higher phylogenetic levels. Using a combination of metabolomic and genomic assays along with ecologically relevant phenotypic screens for bioactivity, we have begun to understand some of the genetic mechanisms underlying this diversity. Preliminary results have illustrated, for example, how structurally closely related molecules can be produced by biosynthetic pathways clustered on the chromosome, biosynthetic pathways clustered on plasmids, and split pathways on plasmids.
