Genome-informed Discovery of Monchicamides A–K:\nCyanobactins from the Microcoleaceae Cyanobacterium LEGE 16532

Genome mining has emerged as an important\ntool for the discovery\nof natural products and is particularly effective for the swift identification\nof ribosomally synthesized and post-translationally modified peptides\n(RiPPs). Among RiPPs, cyanobactins have gained attention due to their\ndiverse structures and bioactive properties. Here, we explored the\nMicrocoleaceae cyanobacterium LEGE 16532 strain and identified the <i>mon</i> biosynthetic gene cluster (BGC), which was predicted\nto encode cyanobactin-like molecules. This led to the detection of\n11 macrocyclic cyanobactins, the monchicamides, some of which feature\nmono- or diprenylation. One of the compounds was isolated, monchicamides\nI (<b>9</b>), and its planar structure was established by LC-HRESIMS/MS\ndata as well as 1D and 2D NMR spectroscopy, confirming forward O-prenylation\nin Tyr. In addition, the absolute configuration of compound <b>9</b> was determined by Marfey’s method and chiral-phase\nHPLC. The structures of the additional cyanobactins were proposed\nfrom MS/MS data analysis. The bioactivity profile of the isolated\ncompound was also evaluated, but no cytotoxic, antimicrobial, or antiamoebic\nactivity was observed.