Natural Products from isnA-Containing Biosynthetic Gene Clusters Recovered from the Genomes of Cultured and Uncultured Bacteria

The sequence of an isonitrile synthase, isnA, was used to search fully sequenced bacterial genomes as well as DNA extracted directly from environmental samples for operons that might use isnA homologues in the biosynthesis of new natural products. This manuscript describes the biosynthetic operons that were found and the compounds that were produced from the heterologous expression of these operons. The identification of new metabolites from the expression of this family of operons suggests that the activation of even simple, sequenced natural product biosynthetic gene clusters using standard E. coli protein expression vectors will be a rewarding and straightforward strategy for the discovery of structurally novel metabolites.