Cylindrospermopsin is a cytotoxin produced by Cylindrospermopsis raciborskii and other cyanobacteria that has been implicated in human intoxications. We report here the complete sequence of the gene cluster responsible for the biosynthesis of this toxin in Oscillatoria sp. strain PCC 6506. This cluster of genes was found to be homologous with that of C. raciborskii but with a different gene organization. Using an enzyme-linked immunosorbent assay and an optimized liquid chromatography analytical method coupled to tandem mass spectrometry, we detected 7-epicylindrospermopsin, cylindrospermopsin, and 7-deoxycylindrospermopsin in the culture medium of axenic Oscillatoria PCC 6506 at the following relative concentrations: 68.6%, 30.2%, and 1.2%, respectively. We measured the intracellular and extracellular concentrations, per mg of dried cells of Oscillatoria PCC 6506, of 7-epicylindrospermopsin (0.18 g/mg and 0.29 g/mg, respectively) and cylindrospermopsin (0.10 g/mg and 0.11 g/mg, respectively). We showed that these two toxins accumulated in the culture medium of Oscillatoria PCC 6506 but that the ratio (2.5 ؎ 0.3) was constant with 7-epicylindrospermopsin being the major metabolite. We also determined the concentrations of these toxins in culture media of other Oscillatoria strains, PCC 6407, PCC 6602, PCC 7926, and PCC 10702, and found that, except for PCC 6602, they all produced 7-epicylindrospermopsin and cylindrospermopsin, with the former being the major toxin, except for PCC 7926, which produced very little 7-epicylindrospermopsin. All the cylindrospermopsin producers studied gave a PCR product using specific primers for the amplification of the cyrJ gene from genomic DNA.Cyanobacteria are known to produce a wide range of secondary metabolites (19), some of which are toxic to humans and animals, and cyanobacterial blooms are frequently associated with human-or animal-poisoning events. Several classes of cyanobacterial toxins have so far been identified, including hepatotoxins, neurotoxins, cytotoxins, and irritants (42). Cases of animal intoxication due to cyanobacterial toxin exposure are regularly reported in different places around the world, and it is now recognized that the release of cyanobacterial toxins in water reservoirs and water supplies has major implications for public health and for the environment (8). For instance, anatoxin-a and homoanatoxin-a, two cyanobacterial neurotoxins, provoke the rapid death of animals by acute asphyxia when ingested, because these alkaloids are potent agonists of the nicotinic acetylcholine receptor (6,11,43,44).In 1979, a significant human-poisoning incident was reported on Palm Island in Australia (14, 16). Afterwards, it was shown that the compound responsible for that poisoning was cylindrospermopsin (CYN) (Fig. 1) and that this cytotoxic molecule was produced by a cyanobacterium, Cylindrospermopsis raciborskii (28). Since then, it was shown that this molecule is also produced by cyanobacteria belonging to other genera such as Anabaena (38), Aphanizomenon (1, ...
