Natural products from the microbial world have provided modern society with some of the most useful medicinal drugs, especially in the area of antimicrobials. In the early period of successful antibiotic discovery from microbes, broad-spectrum bioactive compounds were favoured, as they could be approved for a much larger range of indications. However, in recent years, the recognition that these agents can damage host microbiota and prompt infections with other pathogens has led to renewed interest in narrow-spectrum antimicrobials. One such group of narrow-spectrum antimicrobials is the nargenicin-like macrolides, which were first reported in 1980. This family comprises a group of bacterial natural products with a rare ether bridged cis-decalin moiety. Recently, the enzyme family responsible for the syntheses of these agents has been identified as non-heme iron and α-ketoglutarate (α-KG) dependent oxygenases. We have examined three such enzymes: NarN, StmO3 and BraN, which catalyse the synthesis of the antimicrobials nargenicin, streptoseomycin and branimycin [1, 2]. This presentation will describe the structural characterisation of these enzymes with a particular focus on the molecular origins of their extraordinary activities and specificities.