Aeruginosin 525 (AER525) from Cyanobacterium Aphanizomenon Sp. (KUCC C2): A New Serine Proteases Inhibitor

Aeruginosins (AERs) are one of the most common classes of cyanobacterial peptides synthesised through a hybrid non-ribosomal peptide synthase/polyketide synthase pathway. They have been found in <i>Microcystis</i>, <i>Nodularia spumigena</i>, <i>Oscillatoria</i>/<i>Plantothrix</i>, and <i>Nostoc.</i> The presence of AER in <i>Aphanizomenon</i> isolated from the Curonian Lagoon was reported for the first time in our previous work. Here, the structure of aeruginosin 525 (AER525), isolated from <i>Aphanizomenon</i> sp. KUCC C2, was characterised based on high-resolution mass spectrometry. This new AER variant shows potent activity against thrombin. It also inhibits trypsin and carboxypeptidase A but has no effect on elastase and chymotrypsin. In terms of the <i>N</i>-terminal residue and biological activity, AER525 displaces some similarity to dysinosins, which belongs to the most potent inhibitors of thrombin among AERs. The findings underline the potential of AER525 as a new anticoagulant agent.