289
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      On the Chemistry, Toxicology and Genetics of the Cyanobacterial Toxins, Microcystin, Nodularin, Saxitoxin and Cylindrospermopsin

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The cyanobacteria or “blue-green algae”, as they are commonly termed, comprise a diverse group of oxygenic photosynthetic bacteria that inhabit a wide range of aquatic and terrestrial environments, and display incredible morphological diversity. Many aquatic, bloom-forming species of cyanobacteria are capable of producing biologically active secondary metabolites, which are highly toxic to humans and other animals. From a toxicological viewpoint, the cyanotoxins span four major classes: the neurotoxins, hepatotoxins, cytotoxins, and dermatoxins (irritant toxins). However, structurally they are quite diverse. Over the past decade, the biosynthesis pathways of the four major cyanotoxins: microcystin, nodularin, saxitoxin and cylindrospermopsin, have been genetically and biochemically elucidated. This review provides an overview of these biosynthesis pathways and additionally summarizes the chemistry and toxicology of these remarkable secondary metabolites.

          Related collections

          Most cited references108

          • Record: found
          • Abstract: found
          • Article: not found

          GDSL family of serine esterases/lipases.

          GDSL esterases and lipases are hydrolytic enzymes with multifunctional properties such as broad substrate specificity and regiospecificity. They have potential for use in the hydrolysis and synthesis of important ester compounds of pharmaceutical, food, biochemical, and biological interests. This new subclass of lipolytic enzymes possesses a distinct GDSL sequence motif different from the GxSxG motif found in many lipases. Unlike the common lipases, GDSL enzymes do not have the so called nucleophile elbow. Studies show that GDSL hydrolases have a flexible active site that appears to change conformation with the presence and binding of the different substrates, much like the induced fit mechanism proposed by Koshland. Some of the GDSL enzymes have thioesterase, protease, arylesterase, and lysophospholipase activity, yet they appear to be the same protein with similar molecular weight ( approximately 22-60 kDa for most esterases), although some have multiple glycosylation sites with higher apparent molecular weight. GDSL enzymes have five consensus sequence (I-V) and four invariant important catalytic residues Ser, Gly, Asn, and His in blocks I, II, III, and V, respectively. The oxyanion structure led to a new designation of these enzymes as SGNH-hydrolase superfamily or subfamily. Phylogenetic analysis revealed that block IIA which belonged to the SGNH-hydrolases was found only in clade I. Therefore, this family of hydrolases represents a new example of convergent evolution of lipolytic enzymes. These enzymes have little sequence homology to true lipases. Another important differentiating feature of GDSL subfamily of lipolytic enzymes is that the serine-containing motif is closer to the N-terminus unlike other lipases where the GxSxG motif is near the center. Since the first classification of these subclass or subfamily of lipases as GDSL(S) hydrolase, progress has been made in determining the consensus sequence, crystal structure, active site and oxyanion residues, secondary structure, mechanism of catalysis, and understanding the conformational changes. Nevertheless, much still needs to be done to gain better understanding of in vivo biological function, 3-D structure, how this group of enzymes evolved to utilize many different substrates, and the mechanism of reactions. Protein engineering is needed to improve the substrate specificity, enantioselectivity, specific activity, thermostability, and heterologous expression in other hosts (especially food grade microorganisms) leading to eventual large scale production and applications. We hope that this review will rekindle interest among researchers and the industry to study and find uses for these unique enzymes.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The toxicology of microcystins.

            Microcystins are a family of more than 50 structurally similar hepatotoxins produced by species of freshwater cyanobacteria, primarily Microcystis aeruginosa. They are monocyclic heptapeptides, characterised by some invariant amino acids, including one of unusual structure which is essential for expression of toxicity. Microcystins are chemically stable, but suffer biodegradation in reservoir waters. The most common member of the family, microcystin-LR (L and R identifying the 2 variable amino acids, in this case leucine and arginine respectively) has an LD50 in mice and rats of 36-122 microg/kg by various routes, including aerosol inhalation. Although human illnesses attributed to microcystins include gastroenteritis and allergic/irritation reactions, the primary target of the toxin is the liver, where disruption of the cytoskeleton, consequent on inhibition of protein phosphatases 1 and 2A, causes massive hepatic haemorrhage. Microcystins are tight-binding inhibitors of these protein phosphatases, with inhibition constants in the nanomolar range or lower. Uptake of microcystins into the liver occurs via a carrier-mediated transport system, and several inhibitors of uptake can antagonise the toxic effects of microcystins. The most effective of these is the antibiotic rifampin (a drug approved for clinical use), which protects mice and rats against microcystin-induced lethality when given prophylactically and, in some cases, therapeutically.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Ecotoxicological effects of selected cyanobacterial secondary metabolites: a short review.

              Cyanobacteria are one of the most diverse groups of gram-negative photosynthetic prokaryotes. Many of them are able to produce a wide range of toxic secondary metabolites. These cyanobacterial toxins can be classified in five different groups: hepatotoxins, neurotoxins, cytotoxins, dermatotoxins, and irritant toxins (lipopolysaccharides). Cyanobacterial blooms are hazardous due to this production of secondary metabolites and endotoxins, which could be toxic to animals and plants. Many of the freshwater cyanobacterial blooms include species of the toxigenic genera Microcystis, Anabaena, or Plankthotrix. These compounds differ in mechanisms of uptake, affected organs, and molecular mode of action. In this review, the main focus is the aquatic environment and the effects of these toxins to the organisms living there. Some basic toxic mechanisms will be discussed in comparison to the mammalian system.
                Bookmark

                Author and article information

                Journal
                Mar Drugs
                MD
                Marine Drugs
                Molecular Diversity Preservation International
                1660-3397
                2010
                10 May 2010
                : 8
                : 5
                : 1650-1680
                Affiliations
                [1 ] School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia; E-Mails: leanne.pearson@ 123456unsw.edu.au (L.P.); troco@ 123456unsw.edu.au (T.M.)
                [2 ] School of Biomedical and Health Sciences, The University of Western Sydney, Campbelltown, NSW, 2560, Australia; E-Mail: M.Moffitt@ 123456uws.edu.au (M.M.)
                [3 ] Department of Molecular Biology, The University of Bergen, P.O. Box 7803, 5020 Bergen, Norway; E-Mail: Ralf.Kellmann@ 123456mbi.uib.no (R.K.)
                Author notes
                * Author to whom correspondence should be addressed; E-Mail: b.neilan@ 123456unsw.edu.au ; Tel.: +61-2-9385-3235; Fax: +61-2-9385-1483.
                Article
                marinedrugs-08-01650
                10.3390/md8051650
                2885083
                20559491
                f1d13eaf-9190-452b-9556-1a8bd2db162e
                © 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 26 March 2010
                : 2 May 2010
                : 6 May 2010
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                toxicology,cyanotoxin,non-ribosomal peptide,polyketide,alkaloid

                Comments

                Comment on this article