Nodularin, Microcystin, and the Configuration of Adda.
About: This article is published in ChemInform.The article was published on 1989-03-21. It has received 90 citations till now. The article focuses on the topics: Nodularin & Microcystin.
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TL;DR: The ability of Microcystis assemblages to minimize their mortality losses by resisting grazing by zooplankton and bivalves, as well as viral lysis, and discuss factors facilitating assemblage resilience are highlighted.
704 citations
Cites background from "Nodularin, Microcystin, and the Con..."
...Different microcystin congeners vary in toxicity from essentially non-toxic (e.g., [(6Z)-Adda5] microcystin-LR,LD50 > 1200 mg kg 1) to highly toxic (e.g., microcystin-LR, LD50 = 50 mg kg 1; Rinehart et al., 1994)....
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...Microcystins are cyclic heptapeptides which contain a unique b-amino acid, Adda (3-amino-9-methoxy2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid; Rinehart et al., 1988; Tillett et al., 2000)....
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TL;DR: The hepatotoxicity of microcystins and nodularin may result from inhibition of protein phosphatases and the increase of phosphoproteins, which is similar to that of okadaic acid in the nanomolar range of concentration.
Abstract: Microcystins and nodularin, isolated from toxic blue-green algae, are hepatotoxic monocyclic polypeptides. Both microcystins and nodularin inhibited in vitro protein phosphatase activity present in a cytosolic fraction of mouse liver, bound to the okadaic acid receptors, protein phosphatases 1 and 2A, and thus resulted in the increase of phosphoproteins; this was referred to as the apparent “activation” of protein kinases. Their concentrations causing 50% of the maximal effects are comparable to that of okadaic acid, a potent protein phosphatase inhibitor and a potent tumor promoter, in the nanomolar range of concentration. The increase of phosphoproteins was observed in rat primary cultured hepatocytes and was subsequently associated with morphological changes, which appeared to be a step in the process of hepatotoxicity. The well-known hepatotoxic compounds,α-amanitin and phalloidin, did not show any effects similar to those of microcystins, nodularin and okadaic acid. It is suggested that the hepatotoxicity of microcystins and nodularin may result from inhibition of protein phosphatases and the increase of phosphoproteins.
568 citations
TL;DR: Nearly 30 new microcystins have been isolated in the laboratory from cyanobacteria species and their structures assigned, largely employing tandem FAB mass spectrometry (FABMS/CID/MS) and numerous analogs identified or synthesized allow the identification of important parameters in a structure-activity relationship study.
Abstract: Microcystis andNodularia species produce cyclic hepta- and pentapeptides, microcystins and nodularin, respectively, both containing the same unusual C20 amino acid, abbreviated Adda. Biosynthesis of nodularin fromNodularia and especially of Adda employs a pathway similar to that employed byMicrocystis for producting microcystins. Nearly 30 new microcystins have been isolated in our laboratory from cyanobacteria species and their structures assigned, largely employing tandem FAB mass spectrometry (FABMS/CID/MS). Acyclic peptides, some of them presumed precursors of nodularin and microcystins, have now been isolated and characterized. The numerous analogs identified or synthesized allow the identification of important parameters in a structure-activity relationship study.
475 citations
TL;DR: The different responses of A. flos-aquae and N. spumigena to changes in salinity, irradiance, and temperature may explain the different spatial and temporal distribution of these species in the Baltic Sea.
Abstract: In late summer, nitrogen-fixing cyanobacteria Nodularia spumigena and Aphanizomenon flos-aquae form blooms in the open Baltic Sea. N. spumigena has caused several animal poisonings, but Baltic A. flos-aquae is not known to be toxic. In this laboratory study, performed with batch cultures, the influences of environmental conditions on the biomass and nitrogen fixation rate of N. spumigena and A. flos-aquae were compared and the toxin (nodularin) concentration produced by N. spumigena was measured. Several differences in the biomasses and nitrogen fixation rates of N. spumigena and A. flos-aquae were observed. A. flos-aquae preferred lower irradiances, salinities, and temperatures than N. spumigena. The biomass of both species increased with high phosphate concentrations and with accompanying bacteria and decreased with unnaturally high inorganic nitrogen concentrations. Nodularin concentrations in cells and growth media, as well as nitrogen fixation rates, were generally highest under the conditions that promoted growth. Intracellular nodularin concentrations increased with high temperature, high irradiance, and high phosphate concentration and decreased with low and high salinities and high inorganic nitrogen concentrations. Nodularin concentrations in growth media increased with incubation time, indicating that intracellular nodularin was released when cells lysed. The different responses of A. flos-aquae and N. spumigena to changes in salinity, irradiance, and temperature may explain the different spatial and temporal distribution of these species in the Baltic Sea. According to the results, toxic N. spumigena blooms may be expected in late summer in areas of the Baltic Sea with high phosphorus concentrations and moderate salinity.
296 citations
Cites background from "Nodularin, Microcystin, and the Con..."
...spumigena produces nodularin, a cyclic pentapeptide hepatotoxin with the structure of cyclo(-D-erythro-b-methyl-Asp-LArg-Adda-D-Glu-N-methyldehydro-b-aminobutyric acid), in which Adda is (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (29, 36)....
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TL;DR: The current knowledge regarding the metabolic pathways and enzymes involved in the production of a number of natural products, including the approved antibiotic fosfomycin, the widely used herbicide phosphinothricin (PT), and the clinical candidate for treatment of malaria FR-900098, is presented.
Abstract: Natural products containing carbon-phosphorus bonds (phosphonic and phosphinic acids) have found widespread use in medicine and agriculture. Recent years have seen a renewed interest in the biochemistry and biology of these compounds with the cloning of the biosynthetic gene clusters for several family members. This review discusses the commonalities and differences in the molecular logic that lie behind the biosynthesis of these compounds. The current knowledge regarding the metabolic pathways and enzymes involved in the production of a number of natural products, including the approved antibiotic fosfomycin, the widely used herbicide phosphinothricin (PT), and the clinical candidate for treatment of malaria FR-900098, is presented. Many of the enzymes involved in the biosynthesis of these compounds catalyze chemically and biologically unprecedented transformations, and a wealth of new biochemistry has been revealed through their study. These investigations have also suggested new strategies for natural product discovery.
287 citations
Cites background from "Nodularin, Microcystin, and the Con..."
...Interestingly, the revised structure contains a phosphonate analog of dehydroalanine, which is found in many natural products such as the lantibiotics (127), microcystins (128), and thiostrepton (129)....
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