Formicamycins, antibacterial polyketides produced by Streptomyces formicae isolated from African Tetraponera plant-ants

We report a new <i>Streptomyces</i> species named <i>S. formicae</i> that was isolated from the African fungus-growing plant-ant <i>Tetraponera penzigi</i> and show that it produces novel pentacyclic polyketides that are active against MRSA and VRE. The chemical scaffold of these compounds, which we have called the formicamycins, is similar to the fasamycins identified from the heterologous expression of clones isolated from environmental DNA, but has significant differences that allow the scaffold to be decorated with up to four halogen atoms. We report the structures and bioactivities of 16 new molecules and show, using CRISPR/Cas9 genome editing, that biosynthesis of these compounds is encoded by a single type 2 polyketide synthase biosynthetic gene cluster in the <i>S. formicae</i> genome. Our work has identified the first antibiotic from the <i>Tetraponera</i> system and highlights the benefits of exploring unusual ecological niches for new actinomycete strains and novel natural products.