Variation of Cyanobacterial Hepatotoxins in Finland

Sivonen, Kaarina; Namikoshi, Michio; Luukkainen, Raija; Färdig, Michael; Rouhiainen, Leo; Evans, William; Carmichael, Wayne W.; Rinehart, Kenneth L.; Niemelä, Seppo

doi:10.1533/9781845698164.2.152

Cited by 28 publications

(26 citation statements)

References 13 publications

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“…Genomic DNA was extracted from 36 strains of the filamentous heterocystous genera Anabaena, Nodularia, and Nostoc, the filamentous genus Planktothrix, and the unicellular genus Microcystis (Table 1, which is published as supporting information on the PNAS web site). Just two strains of the genus Nostoc are known to produce microcystins (25,26), one of which was available for this study.…”

Section: Methodsmentioning

confidence: 99%

Phylogenetic evidence for the early evolution of microcystin synthesis

Rantala

Fewer

Hisbergues

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

454

373

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Cyanobacteria are a prolific source of secondary metabolites, including compounds with toxic and enzyme-inhibiting activities. Microcystins and nodularins are the end products of a secondary metabolic pathway comprised of mixed polyketide synthases and nonribosomal peptide synthetases. Both peptides are potent natural toxins produced by distantly related genera of cyanobacteria. Horizontal gene transfer is thought to play a role in the sporadic distribution of microcystin producers among cyanobacteria. Our phylogenetic analyses indicate a coevolution of housekeeping genes and microcystin synthetase genes for the entire evolutionary history of the toxin. Hence they do not corroborate horizontal transfer of genes for microcystin biosynthesis between the genera. The sporadic distribution of microcystin synthetase genes in modern cyanobacteria suggests that the ability to produce the toxin has been lost repeatedly in the more derived lineages of cyanobacteria. The data we present here strongly suggest that the genes encoding nodularin synthetase are recently derived from those encoding microcystin synthetase.

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Section: Methodsmentioning

confidence: 99%

Phylogenetic evidence for the early evolution of microcystin synthesis

Rantala

Fewer

Hisbergues

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

454

373

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“…The unicellular freshwater species Microcystis aeruginosa is an exceptionally rich source of peptide metabolites and has been given much attention as the cause of serious health problems in humans and livestock (Carmichael, 1994;Sivonen et al, 1995). Microcystins (MCYSTs) are cyclic heptapeptides that share the common structure cyclo(-D -Ala-L-X-D -MeAsp-L-Z-Adda-DGlu-Mdha), where X and Z are variable L-amino acids, Adda is (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid, D-MeAsp is D-erythro-␤-iso-aspartic acid, and Mdha is N-methyl-dehydroalanine (Fig.…”

Section: Introductionmentioning

confidence: 99%

Insertional mutagenesis of a peptide synthetase gene that is responsible for hepatotoxin production in the cyanobacterium Microcystis aeruginosa PCC 7806

Dittmann

Neilan

Erhard³

et al. 1997

Molecular Microbiology

370

326

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SummarySeveral bloom-forming cyanobacterial genera produce potent inhibitors of eukaryotic protein phosphatases called microcystins. Microcystins are hepatotoxic cyclic heptapeptides and are presumed to be synthesized non-ribosomally by peptide synthetases. We identified putative peptide synthetase genes in the microcystin-producing strain Microcystis aeruginosa PCC 7806. Non-hepatotoxic strains of M. aeruginosa lack these genes. Strain PCC 7806 was transformed to chloramphenicol resistance. The antibiotic resistance cassette insertionally inactivated a peptide synthetase gene of strain PCC 7806 as revealed by Southern hybridization and DNA amplification. This is the first report of genetic transformation and mutation, by homologous recombination, of a bloomforming cyanobacterium. Chemical and enzymatic analyses, including high-performance liquid chromatography (HPLC), mass spectrometry, amino acid activation, and protein phosphatase inhibition, revealed the inability of derived mutant cells to produce any variant of microcystin while maintaining their ability to synthesize other small peptides. The disrupted gene therefore encodes a peptide synthetase (microcystin synthetase) that is specifically involved in the biosynthesis of microcystins. Our results confirm that microcystins are synthesized non-ribosomally and that a basic difference between toxic and nontoxic strains of M. aeruginosa is the presence of one or more genes coding for microcystin synthetases.

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“…We have surveyed the distribution of toxin-producing cyanobacterium strains in Finnish lakes (31) and purified and characterized many of the toxins (28)(29)(30). Recently, we brought a number of these strains into axenic culture.…”

mentioning

confidence: 99%

Characterization of toxin-producing cyanobacteria by using an oligonucleotide probe containing a tandemly repeated heptamer

et al. 1995

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Cyanobacteria produce toxins that kill animals. The two main classes of cyanobacterial toxins are cyclic peptides that cause liver damage and alkaloids that block nerve transmission. Many toxin-producing strains from Finnish lakes were brought into axenic culture, and their toxins were characterized. Restriction fragment length polymorphism analysis, probing with a short tandemly repeated DNA sequence found at many locations in the chromosome of Anabaena sp. strain PCC 7120, distinguishes hepatotoxic Anabaena isolates from neurotoxin-producing strains and from Nostoc spp.

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Variation of Cyanobacterial Hepatotoxins in Finland

Cited by 28 publications

References 13 publications

Phylogenetic evidence for the early evolution of microcystin synthesis

Phylogenetic evidence for the early evolution of microcystin synthesis

Insertional mutagenesis of a peptide synthetase gene that is responsible for hepatotoxin production in the cyanobacterium Microcystis aeruginosa PCC 7806

Characterization of toxin-producing cyanobacteria by using an oligonucleotide probe containing a tandemly repeated heptamer

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