Structural Diversity, Characterization and Toxicology of Microcystins

Abstract

Hepatotoxic microcystins (MCs) are the most widespread class of cyanotoxins and the one that has most often been implicated in cyanobacterial toxicosis. One of the main challenges in studying and monitoring MCs is the great structural diversity within the class. The full chemical structure of the first MC was elucidated in the early 1980s and since then, the number of reported structural analogues has grown steadily and continues to do so, thanks largely to advances in analytical methodology. The structures of some of these analogues have been definitively elucidated after chemical isolation using a combination of techniques including nuclear magnetic resonance, amino acid analysis, and tandem mass spectrometry (MS/MS). Others have only been tentatively identified using liquid chromatography-MS/MS without chemical isolation. An understanding of the structural diversity of MCs, the genetic and environmental controls for this diversity and the impact of structure on toxicity are all essential to the ongoing study of MCs across several scientific disciplines. However, because of the diversity of MCs and the range of approaches that have been taken for characterizing them, comprehensive information on the state of knowledge in each of these areas can be challenging to gather. We have conducted an in-depth review of the literature surrounding the identification and toxicity of known MCs and present here a concise review of these topics. At present, at least 279 MCs have been reported and are tabulated here. Among these, about 20% (55 of 279) appear to be the result of chemical or biochemical transformations of MCs that can occur in the environment or during sample handling and extraction of cyanobacteria, including oxidation products, methyl esters, or post-biosynthetic metabolites. The toxicity of many MCs has also been studied using a range of different approaches and a great deal of variability can be observed between reported toxicities, even for the same congener. This review will help clarify the current state of knowledge on the structural diversity of MCs as a class and the impacts of structure on toxicity, as well as to identify gaps in knowledge that should be addressed in future research.

Salt Shock Responses of Microcystis Revealed through Physiological, Transcript, and Metabolomic Analyses

“…In addition, Microcystis has been particularly well studied because of its ability to produce the hepatotoxin microcystin (MC). Indeed, with nearly 279 MC variants described in the literature [2], the occurrence of MCs in aquatic ecosystems represents a threat to both human and animal health [3]. Within the Microcystis genus, the species M. aeruginosa has received particular attention, being the dominant species in blooms worldwide [1,4].…”

Metabolome Variation between Strains of Microcystis aeruginosa by Untargeted Mass Spectrometry

“…In addition, other factors including global warming, changes in hydrology, and pesticide use may be acting synergistically to accelerate cyanobacterial blooms [1,[5][6][7][8]. These blooms can also be harmful since cyanobacteria have the potential to produce a range of toxins, including hepatotoxins, neurotoxins, and endotoxins [9,10]. In 1996, 60 patients died due to acute neurotoxicity and subacute hepatotoxicity in Caruaru, Brazil, after hemodialysis treatments using cyanobacteria-contaminated water [11].…”

“…Despite many ecological impacts, the biological role of MCs within cyanobacteria remains unknown, which makes their control difficult. Remarkably, the cell concentrations of MCs in toxigenic taxa can reach those of chlorophyll a [22], the primary pigment involved in photosynthesis in cyanobacteria, algae and higher plants.Thus far over 269 variants have been identified with molecular weights varying between 880 and 1200 Da [10,23]. Amino acid variation in various positions of the cyclic molecule affects the degree of toxicity in vertebrates, as shown by LD 50 values between 50 µg/kg (MC-LA) and 800 µg/kg (MC-RR) in mice after intraperitoneal injection [16].…”

“…Thus far over 269 variants have been identified with molecular weights varying between 880 and 1200 Da [10,23]. Amino acid variation in various positions of the cyclic molecule affects the degree of toxicity in vertebrates, as shown by LD 50 values between 50 µg/kg (MC-LA) and 800 µg/kg (MC-RR) in mice after intraperitoneal injection [16].…”

Cylindrospermopsin- and Deoxycylindrospermopsin-Producing Raphidiopsis raciborskii and Microcystin-Producing Microcystis spp. in Meiktila Lake, Myanmar

“…The reason for this is that the response in LCMS can be expected to vary from congener-to-congener, primarily due to variations in the number of easily ionisable amino acid residues, especially Arg, present in the MC's structure. Only the identification of previously unreported MCs (see Bouaïcha et al [35]) in the cultures is discussed further (i.e., 7, 9, 19, 22, 24, 27, 30-35, 37, 38, 40, 42, 46, 51-53, 55 and 56) but spectra of all compounds Table 4 (see Table S1 for positive ionisation m/z values). Note that some of the smaller peaks are not labelled on the chromatograms, and the peak marked with an asterisk is not from a MC.…”