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Biologically active cyanobacteria metabolites – Ecological and biomedical perspectives
The hepatotoxic microcystins are the most frequently monitored toxins in cyanobacteria waterblooms. Microcystins are produced by several genera of cyanobacteria, including Microcystis, Anabeana, Nostoc and Planktothrix (Oscillatoria). More than seventy natural variants of these cyclic peptides are known. The major toxins found in various species of these genera are: microcystin-LR, microcystin-YR, as well as microcystin-RR. The microcystins are stable in the mammalian gastrointestinal system and are absorbed in the gastrointestinal tract, transported to the liver and concentrated there. Within the liver cells, the microcystins, inhibit specific protein phosphatases (PPs), PP1 and PP2, which are key components for the control of the cell structure and function, with IC50's that vary between 0.1 nM and 10 nM. The appearance of toxicity by microcystins depends on the balance between their accumulation and metabolism in the liver. Comparisons of the toxicity of pure microcystins with the toxicity of intact cells from toxic cyanobacteria-blooms, or their crude extracts, suggest that other compounds that accompany the microcystins enhance their activity. The microcystins, are usually accompanied by a considerable amount of protease inhibitors from five different groups, namely – micropeptins, aerugenosins, microginins, anabaenopeptins and microveridins. The biological activity and structure/activity relationships of these groups of protease inhibitors, as well as the relationships between the toxicity of the microcystins and the protease inhibitors and some possible involvement of these metabolites with cyanobacterial bloom collapse, are presented.