Microcystins

Microcystins are a group of cyclic heptapeptide (7 amino acids) hepatotoxins (liver toxins) produced by a number of cyanobacterial genera, the most notable of which is the widespread Microcystis from which the toxins take their name. Microcystins have been reported in this organism and other cyanobacteria world- wide. There have been approximately 60 different microcystins identified to date. Microcystins consist of a seven-membered peptide ring which is made up of five non-protein amino acids and two protein amino acids. It is these two protein amino acids that distinguish microcystins from one another, while the other amino acids are more or less constant between variant microcystins. Using amino acid single letter code nomenclature, each microcystin is designated a name depending on the variable amino acids which complete their structure. The most common and potently toxic microcystin-LR contains the amino acids Leucine (L) and Arginine (R) in these variable positions. Below is the general stucture of microcystins showing the variable amino acid positions "X" and "Z". The amino acids are delineated in this diagram and numbered according to the microcystin standard nomenclature. R1 and R2 are H in demethylated microcystins.

The molecular structure of microcystin-LR can be seen below, with the variable amino acids leucine and arginine in Blue and Purple respectively.

View an ANIMATION of MCYST-LR. The "Adda" amino acid has become a useful tool in microcystin research as it provides the molecule with a characterstic wavelength absorbance at 238 nm. This is believed to be attributable to the conjugated diene group in the long carbon chain of this uncommon amino acid. The Adda moiety is also required for toxicity and is important in the binding of the toxin to PROTEIN PHOSPHATASES. The stereochemistry about the dienes of the Adda group have also been shown to influence toxicity, as too have the levels of methylation of various structures in the cyclic peptide. As such, the relative toxicities of microcystins can differ greatly. The absorbance characteristics of Adda provide a means of analysis of microcystins after separating them by reverse phase HPLC.

Nodularin

The first scientific report of the potent toxicity of cyanobacterial blooms was made in Nature by George Francis in 1878. The author reported that stock deaths had occurred as a result of drinking from a bloom infested lake in Australia. The organism resposible for this bloom was later described as Nodularia spumigena and the toxin has since been isolated and characterised (Rinehart et al., 1988*) as "Nodularin." The structure of nodularin is related to the potent cyclic heptapeptide hepatotoxins, theMICROCYSTINS, but differs in that nodularin is composed of only five amino acids in the peptide ring. Not only are the stucture of these two cyanobacterial toxins similar, but they both show the same hepatotoxic effect through the potent inhibition of PROTEIN PHOSPHATASES and similar IC50 and LD50 values.

*Rinehart, K. L., K. Harada, M. Namikoshi, C. Chen, and C. A. Harvis. 1988. Nodularin, microcystin and the configuration of Adda. J. Am. Chem. Soc. 110(25):8557-8558.

Anatoxins
Anatoxins are a group of neurotoxic alkaloids produced by a number of cyanobacterial genera includingAnabaena, Oscillatoria and Aphanizomenon. The toxicity of these compounds (LD50)varies from 20 g kg-1(by weight, I.P. mouse) for anatoxin-a(S) to 200-250 g kg-1 for anatoxin-a and homoanatoxin-a, making them more toxic than many MICROCYSTINS.

Saxitoxins
Like anatoxins, the saxitoxins (STX) are neurotoxic alkaloids which are also known as PSP's (paralytic shelfish poisons) due to their occurance and association with seafood. They block sodium channels in nerve cells, thus casuing their neurotoxic effects. There are a number of STX variants generally divided into groups based on their structure or organism of origin. The single sulphated STX's are known as gonyautoxins (GTX) and the doubly sulphated STX's are known as C-toxins. There are also decarbamyl STX's (dcSTX) and a group of STX variants, so far found only in Lyngbya wollei, known as Lyngbya-wollei-toxins (LWTX). STX's are highly toxic with LD50's as low as 10 g kg-1 (i.p.) in mice. The STX family has the following general structure.

Cylindrospermopsin
Although originally described from Cylindrospermopsis raciborskii, cylindrospermopsin can be found also in Aphanizomenon ovalisporum and Umezakia natans. The toxin is a cyclic alkaloid and, like microcystins, primarily affects the liver, although causes considerable damage to other major organs. Its LD50 (i.p., mice) of 200 g kg-1ranks it as a relatively potent cyanobacterial toxin.

Lyngbyatoxin a
This indole alkaloid toxin is related to teleocidin B from Streptomyces. It is produced by Lyngbya majuscula. The toxin is highly inflammatory and vesicatory. It is the causative agent of seaweed dermatitis. It is also a strong tumor promoter through activation of protein kinase C.

Aplysiatoxins

Produced by marine cyanobacteria such as Lyngbya, aplysiatoxins are commonly known for their dermatotoxic activity causing inflamation of the skin. They are also potent tumour promoters. Aplysiatoxins and debromoaplysiatoxin have been found associated with filamentous cyanobacterial species includingSchizothrix calcicola and Oscillatoria nigroviridis.