Isolation and characterization of hepatotoxic microcystin homologs from the filamentous freshwater cyanobacterium Nostoc sp. strain 152

• Published in: Applied and Environmental Microbiology 1990-09, Vol.56 (9), p.2650-2657
• Main Authors: Sivonen, K. (University of Helsinki, Helsinki, Finland), Carmichael, W.W, Namikoshi, M, Rinehart, K.L, Dahlem, A.M, Niemela, S.I
• Format: Article
• Language: English
• Subjects: amino acid composition; Amino Acids - analysis; Aminoacids, peptides. Hormones. Neuropeptides; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; biological poisons; Cyanobacteria - analysis; Finland; FINLANDE; FINLANDIA; FOIE; Fresh Water; Freshwater; Fundamental and applied biological sciences. Psychology; HIGADO; Liver - drug effects; Marine Toxins - isolation & purification; Mice; Microcystins; NOSTOC; PEPTIDE; peptides; Peptides, Cyclic - chemistry; Peptides, Cyclic - isolation & purification; Peptides, Cyclic - toxicity; PEPTIDOS; PESO MOLECULAR; Plants, Toxic; POIDS MOLECULAIRE; PROPIEDADES FISICO-QUIMICAS; PROPRIETE PHYSICOCHIMIQUE; Proteins; toxicity; TOXINAS; TOXINE; toxins
• ISSN: 0099-2240; 1098-5336
• DOI: 10.1128/aem.56.9.2650-2657.1990

A strain of the filamentous cyanobacterium Nostoc sp. isolated from a lake in Finland was found to produce at least nine hepatotoxic peptides with chemical and toxicological properties similar to those of the hepatotoxic hepta- and pentapeptides produced by other cyanobacteria. Toxins were isolated and purified by high-performance liquid chromatography. Amounts available for five of the purified toxins (P6, P14, P15, P16, and P18) were adequate for high-performance liquid chromatography amino acid analysis and determination of molecular weight by fast-atom bombardment-mass spectrometry (FAB-MS). Quantities of three toxins (P14, P15, and P16) were adequate for further analysis by high-resolution FAB-MS, FAB-MS/MS, and H-nuclear magnetic resonance. Analysis showed that the toxins are new types of microcystin-LR homologs. Microcystin-LR contains equimolar amounts of D-alanine, L-leucine, D-erythro-beta-methylaspartic acid, L-arginine, ADDA (3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid), D-glutamic acid, and N-methyldehydroalanine (molecular weight [MW], 994). Nostoc sp. strain 152 was found to produce the following microcystin-LR homologs: (i) P6 contains an extra methylene group most probably due to the presence of N-methyldehydrobutyrine instead of N-methyldehydroalanine (MW, 1,008); (ii) P14 is O-acetyl-O-demethyl ADDA-microcystin-LR (MW, 1,022); (iii) P15 is 3-demethyl-O-acetylADDA-homoarginine-microcystin-LR (MW, 1,036); (iv) P16 is 3-demethyl-O-acetyl-O-demethylADDA-microcystin-LR (MW, 1,008); (v) P18 is 3-demethyl-O-acetyl-O-demethylADDA-homoarginine-microcystin-LR (MW, 1,022). The toxicities of the new microcystin homologs were not significantly different from those of microcystin-LR or demethylmicrocystin-LR