Toxins and biologically active secondary metabolites of Microcystis sp. isolated from Lake Kinneret

For many years cyanobacteria were considered a minor, negligible component of the phytoplankton population in Lake Kinneret (Sea of Galilee, Israel). However, during the last decade several new species invaded the lake and other, more common species were present more frequently and in higher concentrations. Recently, we isolated two Microcystis sp. strains from Lake Kinneret. Both produced an array of hepatotoxic microcystins. In a bioassay-guided study we identified in exudates of one of the Microcystis strains (MB-K) that allelopathic activity was attributed to a novel metabolite, microcarbonin A (1). Subsequently, two other novel metabolites, micropeptin KT946 (2) and anabaenopeptin KT864 (3), were isolated from the hydrophilic extract of the cultured (MB-K) strain, based on their protease inhibition activity. Homo- and heteronuclear-2D-NMR techniques, as well as HRMS, determined the gross structure of the three compounds. The relative and absolute stereochemistry of 2 and 3 was deduced from a combination of spectral data and Marfey's method for HPLC.