https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

This book describes the present state of knowledge regarding the impact of cyanobacteria on health through the use of water. It considers aspects of risk management and details the information needed for protecting drinking water sources and recreational water bodies from the health hazards caused by cyanobacteria and their toxins. It also outlines the state of knowledge regarding the principal considerations in the design of programmes and studies for monitoring water resources and supplies and describes the approaches and procedures used.
The development of this publication was guided by the recommendations of several expert meetings concerning drinking water (Geneva, December 1995; Bad Elster, June
1996) and recreational water (Bad Elster, June 1996; St Helier, May 1997). An expert meeting in Bad Elster, April 1997, critically reviewed the literature concerning the toxicity of cyanotoxins and developed the scope and content of this book. A draft manuscript was reviewed at an editorial meeting in November 1997, and a further draft was
reviewed by the working group responsible for updating the Guidelines for Drinkingwater Quality in March 1998.

/pdf/toxic-cyanobacteria-in-water-a-guide-to-their-public-health-2y64v55hv1.pdf

Toxic cyanobacteria in water: a guide to their public health consequences, monitoring and management.

Cyanobacteria secondary metabolites--the cyanotoxins.

(2002). The Effects of Harmful Algal Blooms on Aquatic Organisms. Reviews in Fisheries Science: Vol. 10, No. 2, pp. 113-390.

The Effects of Harmful Algal Blooms on Aquatic Organisms

Certain waterblooms of toxic cyanobacteria (blue-green algae) are a health threat because of their production of toxic peptides, termed microcystins, which cause liver damage in wild and domesticated animals. The most widely studied microcystin is microcystin-LR, a heptapeptide containing the twol-amino acids, leucine and arginine. The inhibition of protein phosphatase type 1 and type 2A activities by microcystin-LR is similar to that of the known protein phosphatase inhibitor and tumor promoter okadaic acid. We show in this report that microcystin-LR, applied below the acute toxicity level, dose-dependently increases the number and percentage area of positive foci for the placental form of glutathioneS-transferase in rat liver, which was initiated with diethylnitrosamine. The result was obtained independently through two animal experiments. This observation indicates that microcystin-LR is a new liver tumor promoter mediated through inhibition of protein phosphatase type 1 and type 2A activities. This provides further evidence that the okadaic acid pathway is a general mechanism of tumor promotion in various organs, such as mouse skin, rat glandular stomach and rat liver.

https://link.springer.com/content/pdf/10.1007/BF01629424.pdf

Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR.

Three new cyclic heptapeptide hepatotoxins, [D-Ser1,ADMAdda5]microcystin-LR (1), [D-Asp3,-ADMAdda5]microcystin-LHar (2), and [ADMAdda5,Mser7]microcystin-LR (3), were isolated from the cyanobacterium (blue-green alga) Nostoc sp. strain 152, together with four known microcystins, [ADMAdda5]microcystin-LR (4), [ADMAdda5]microcystin-LHar (5), [D-Asp3,-ADMAdda5]microcystin-LR (6), and [DMAdda5]microcystin-LR (7). The structures of new microcystins were assigned on the basis of high-resolution fast atom bombardment mass spectrometry (HR FABMS), collisionally induced tandem FABMS (FABMS/MS), amino acid analysis, and gas chromatography (GC) on a chiral capillary column. All three new toxins contained 9-acetoxy-3-amino-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (ADMAdda) instead of the corresponding 9-methoxyl derivative (Adda), while 7 contains the corresponding 9-hydroxy analog (DMAdda). Compound 1 is the first microcystin reported that contains D-serine (D-Ser) in lieu of the D-alanine (D-Ala) unit which was thought to be an invariable amino acid component of the microcystins. Compound 2 has L-homoarginine (Har) instead of L-arginine (L-Arg) in 6 and D-aspartic acid (D-Asp) instead of D-erythro-beta-methylaspartic acid (D-MeAsp) in 5. Compound 3, the N-methylserine (Mser) variant of the N-methyldehydroalanine unit in 4, would be a biosynthetic precursor of 4.

Three new microcystins, cyclic heptapeptide hepatotoxins, from Nostoc sp. strain 152.

Three new hepatotoxic cyclic heptapeptides in the microcystin class were isolated from the cyanobacterium (blue-green alga) Nostoc sp: strain 152 and assigned structures based on their high-resolution FABMS, FABMS/MS, 1 H and 13 C NMR spectra, amino acid analysis, and GC on a chiral capillary column. All three toxins (1-3) have 9-acetoxy-3-amino-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid as an unusual structural component instead of the corresponding 9-methoxyl derivative (Adda) found in the microcystins

Structures of three new cyclic heptapeptide hepatotoxins produced by the cyanobacterium (blue-green alga) Nostoc sp. strain 152

Four new polysulfur aromatic alkaloids, lissoclibadins 4 (1), 5 (2), 6 (3), and 7 (4), were isolated from the ascidian Lissoclinum cf. badium collected in Indonesia, together with seven known alkaloids, lissoclibadins 1 (5), 2 (6), and 3 (7), lissoclinotoxins E (8) and F (9), 3,4-dimethoxy-6-(2'-N,N-dimethylaminoethyl)-5-(methylthio)benzotrithiane (10), and N,N-dimethyl-5-(methylthio)varacin (11). Compounds 1-11 were isolated from the ascidian collected in March (wet season), while 5-11 have been obtained previously from the organism collected in September (dry season) at the same site. The structures of the new compounds were assigned on the basis of their spectroscopic data. Lissoclibadins 4-7 (1-4) inhibited the colony formation of Chinese hamster V79 cells with EC50 values of 0.71, 0.06, 0.06, and 0.17 microM, respectively. Compounds 1-4 showed also weak antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Saccharomyces cerevisiae.

Lissoclibadins 4−7, Polysulfur Aromatic Alkaloids from the Indonesian Ascidian Lissoclinum cf. badium⊥

A general method has been developed for assigning the structures of nodularin, a potent hepatotoxin, tumor promoter, and protein phosphatase inhibitor, and minor components isolated from a cultured and a bloom sample of the cyanobacterium Nodularia spumigena. It consists of (1) FABMS analysis (determination of molecular weight and molecular formula), (2) 1 H NMR spectroscopy on the parent compound and chiral GC analysis of an acid hydrolyzate (identification and stereochemistry of amino acid components), (3) ozonolysis followed by NaBH 4 reduction (conversion to a linear peptide), and (4) FABMS/CID/MS analyses of the linear peptide and the parent compound (sequence analysis). The method has been employed in assigning structures to three new nodularins (2-4) and can be applied to other cyclic peptides containing α,β-dehydroamino acid unit(s), especially the related microcystins, cyclic heptapeptide hepatotoxins. Two nodularins,[DMAdda 3 ]nodularin (2) and [(6Z)-Adda 3 ]nodularin (3), were obtained from a bloom sample collected from lake Ellesmere (New Zealand), and [D-Asp 1 ]nodularin (4) was isolated from cultured cells (strain L-575). The LD50s of 2 and 4 were 150 and 75 μg/kg (ip, mice), respectively, but 3 did not show apparent toxicity at 2.0 mg/kg

Michio Namikoshi

Papers

Three new microcystins, cyclic heptapeptide hepatotoxins, from Nostoc sp. strain 152.

Structures of three new cyclic heptapeptide hepatotoxins produced by the cyanobacterium (blue-green alga) Nostoc sp. strain 152

Lissoclibadins 4−7, Polysulfur Aromatic Alkaloids from the Indonesian Ascidian Lissoclinum cf. badium⊥

New Nodularins: A General Method for Structure Assignment

Nodularin, Microcystin, and the Configuration of Adda.