Genome-informed Discovery of Monchicamides A-K: Cyanobactins from the Microcoleaceae Cyanobacterium LEGE 16532

Genome mining has emerged as an important tool for the discovery of natural products and is particularly effective for the swift identification of ribosomally synthesized and post-translationally modified peptides (RiPPs). Among RiPPs, cyanobactins have gained attention due to their diverse structures and bioactive properties. Here, we explored the Microcoleaceae cyanobacterium LEGE 16532 strain and identified the mon biosynthetic gene cluster (BGC), which was predicted to encode cyanobactin-like molecules. This led to the detection of 11 macrocyclic cyanobactins, the monchicamides, some of which feature mono- or diprenylation. One of the compounds was isolated, monchicamides I (9), and its planar structure was established by LC-HRESIMS/MS data as well as 1D and 2D NMR spectroscopy, confirming forward O-prenylation in Tyr. In addition, the absolute configuration of compound 9 was determined by Marfey's method and chiral-phase HPLC. The structures of the additional cyanobactins were proposed from MS/MS data analysis. The bioactivity profile of the isolated compound was also evaluated, but no cytotoxic, antimicrobial, or antiamoebic activity was observed.