Skyllamycins D and E, Non-Ribosomal Cyclic Depsipeptides from Lichen-Sourced .

The skyllamycins are a class of heavily modified, non-ribosomal peptides, first isolated from sp. KY11784. A strain with potent antibiotic activity against was isolated from a sample of the New Zealand lichen . Whole genome sequencing and biosynthetic gene cluster genetic analysis coupled with GNPS LCMS/MS molecular networking revealed that this strain had the capacity to produce skyllamycins, including previously undescribed congeners, and that these were likely the source of the observed biological activity. Guided by the results of the molecular networking, we isolated the previously reported skyllamycins A-C (-), along with two new congeners, skyllamycins D () and E (). The structures of these compounds were elucidated using comprehensive 1D and 2D NMR analyses, along with HRESIMS fragmentation experiments. Antibacterial assays revealed that skyllamycin D possessed improved activity against E168 compared to previously reported congeners.