Natural Substances of Marine Origin with Toxic Properties

  • Heike HelmholzEmail author


The marine environment covers more than 70% of the earth surface and is one of the richest biospheres of the world. Biological and chemical investigations of marine ecosystems have provided insights into a fascinating and complex world underwater. The biological and chemical diversity is very high due to the array of natural conditions. It encompasses a high thermal range from −1.5°C to 350°C and a pressure range of 1–1,000 atm. The food conditions vary between nutrient rich and nutritionally sparse regions and photic and non-photic zones. Marine organisms have to adapt to these wide variety of living conditions. The adaptation capabilities are different from those of land-based organisms (Lindequist and Schweder 2001). Marine organisms live in close associations and therefore in nutrition and substrate competition (Ianora et al. 2006). In order to ensure survival and fitness it is necessary to produce secondary metabolites. The variety of secondary metabolites provides a biochemical reflection of the biotic interactions. The function of secondary metabolites is manifold. Allelochemicals are used for intra- and interspecies signaling and communication, for the deterrence of predators and herbivores or the suppression of competing neighbors. Bacterial and fungal invasion can be inhibited. Secondary metabolites can also be used for protection against UV radiation.


Marine Organism Domoic Acid Paralytic Shellfish Poisoning Hooded Seal Cone Snail 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abdiche, Y.N., and D.G. Myszka, 2004: Probing the Mechanism of Drug/Lipid Membrane Interactions Using Biacore. Anal. Biochem. 328, 233–43.CrossRefGoogle Scholar
  2. Anderluh, G., and P. Macek, 2002: Cytolytic Peptide and Protein Toxins from Sea Anemones (Anthozoa: Actiniaria). Toxicon 40, 111–24.CrossRefGoogle Scholar
  3. Anderluh, G, J. Pungercar, B. Struklj, P. Macek, and F. Gubensek, 1996: Cloning, Sequencing, and Expression of Equinatoxin II. Biochem. Biophys. Res. Comm. 230, 437–42.CrossRefGoogle Scholar
  4. Anderluh, G., P. Macek, and J.H. Lakey, 2003: Peeking into a Secret World of Pore-Forming Toxins: Membrane Binding Processes Studied by Surface Plasmon Resonance. Toxicon 42, 225–8.CrossRefGoogle Scholar
  5. Aneiros, A., and A. Garateix, 2004: Bioactive Peptides from Marine Sources: Pharmacological Properties and Isolation Procedures. J. Chromatogr. B 803, 41–53.CrossRefGoogle Scholar
  6. Athanasiadis, A, G. Anderluh, P. Macek, and D. Turk, 2001: Crystal Structure of the Soluble Form of Equinatoxin Ii, a Pore-Forming Toxin from the Sea Anemone Actinia equina. Structure 9, 341–6.CrossRefGoogle Scholar
  7. Bailey, P.M., M. Little, G.A. Jelinek, and J.A. Wilce, 2003: Jellyfish Envenoming Syndroms: Unknown Toxic Mechanisms and Unproven Therapies. Med. J. Aust. 178, 34–7.Google Scholar
  8. Baird, C.L., E.S. Courtenay, and D.G. Myszka, 2002: Surface Plasmon Resonance Characterization of Drug/Liposome Interactions. Anal. Biochem. 310, 93–9.CrossRefGoogle Scholar
  9. Bamstedt, U, M.B. Martinussen, and S. Matsakis, 1994: Trophodynamics of the Two Scyphozoan Jellyfishes, Aurelia aurita and Cyanea capillata, in Western Norway. ICES J. Mar. Sci. 51, 369–82.CrossRefGoogle Scholar
  10. Blunt, J.W., B. Copp, W.P. Hu, M.H.G. Munro, D.H. Northcote, and M.R. Prinsep, 2009: Marine Natural Products. Nat. Prod. Rep. 26, 170–244.CrossRefGoogle Scholar
  11. Bongiorni, L, and F. Pietra, 1996: Marine Natural Products for Industrial Applications. Chem. Ind. 15, 54–8.Google Scholar
  12. Bremer, G., 1997: Marine Microorganisms as a Source of Novel Bioactive Compounds; Current Status, Prospects and Strategies for the Future. In: Marine Microorganisms for Industry. Eds. Y Le Gal and A Muller-Feuga: IFREMER, France.Google Scholar
  13. Brinkman, D., and J. Burnell, 2007: Identification, Cloning and Sequencing of Two Major Venom Proteins from the Box Jellyfish, Chironex fleckeri. Toxicon 50, 850–60.CrossRefGoogle Scholar
  14. Burgess, J.G., E.M. Jordan, M. Bregu, A. Mearns-Spragg, and K.G. Boyd, 1999: Microbial Antagonism: A Neglected Avenue of Natural Products Research. J. Biotech. 70, 27–32.CrossRefGoogle Scholar
  15. Burnett, J.W., 2001: Medical Aspects of Jellyfish Envenomination: Pathogenesis, Case Reporting and Therapy. Hydrobiologia 451, 1–9.CrossRefGoogle Scholar
  16. Butler, A, and J.N. Carter-Franklin, 2004: The Role of Vanadium Bromoperoxidase in the Biosynthesis of Halogenated Marine Natural Products. Nat. Prod. Rep. 21, 180–8.CrossRefGoogle Scholar
  17. Cembella, A.D., G.J. Doucette, and I. Garthwaite, 2003: Vitro Assays for Phycotoxins. In: Manual on Harmful Marine Microalgae. Eds. GM Hallegraeff, DM Anderson and AD Cembella: UNESCO Publishing, France.Google Scholar
  18. Costantino, V., E. Fattorusso, M. Menna, and O. Taglialatela-Scafati, 2004: Chemical Diversity of Bioactive Marine Natural Products: An Illustrative Case Study. Curr. Med. Chem. 11, 1671–92.CrossRefGoogle Scholar
  19. Danelian, E, A. Karlen, R. Karlsson, S. Winiwater, A. Hansson, S. Löfas, H. Lennernäz, and M.D. Hämäläinen, 2000: SPR Biosensor Studies of the Direct Interaction Between 27 Drugs and a Liposome Surface: Correlation with Fraction Absorbed in Humans. J Med. Chem. 43, 2083–6.CrossRefGoogle Scholar
  20. Daranas, A.H., M. Norte, and J.J. Fernandez, 2001: Toxic Marine Microalgae. Toxicon 39, 1101–32.CrossRefGoogle Scholar
  21. Davidson, B.S., 1995: New Dimensions in Natural Products Research: Cultured Marine Microorganisms. Curr. Opin. Biotechnol. 6, 284–91.CrossRefGoogle Scholar
  22. Dembitsky, V.M., and M. Srebnik, 2002: Natural Halogenated Fatty Acids: Their Analogues and Derivatives. Progr. Lipid Res. 41, 315–67.CrossRefGoogle Scholar
  23. Ebada, S.S., R.A. Edrada, W. Lin, and P. Proksch, 2008: Methods for Isolation, Purification and Structural Elucidation of Bioactive Secondary Metabolites from Marine Invertebrates. Nat. Protoc. 3, 1820–31.CrossRefGoogle Scholar
  24. Emura, A, M. Yukihiko, and T. Oda, 2004: Evidence for the Production of a Novel Proteinaceous Hemolytic Exotoxin by Dinoflagellate Alexandrium taylori. Harmful Algae 3, 29–37.CrossRefGoogle Scholar
  25. Engel, S., P.R. Jensen, and W. Fenical, 2002: Chemical Ecology of Marine Microbial Defense. J. Chem. Ecol. 28, 1971–85.CrossRefGoogle Scholar
  26. Gribble, G.W., 2003: Naturally Occurring Halogenated Pyrroles and Indoles. Prog. Heterocyc. Chem. 15, 58–74.CrossRefGoogle Scholar
  27. Halstvedt, C.B., T. Rohrlack, R. Ptacnik, and B. Edvardsen, 2008: On the Effect of Abiotic Environmental Factors on Production of Bioactive Oligopeptides in Field Populations of Planktothrix spp. (Cyanobacteria). J. Plankton Res. 30, 607–17.CrossRefGoogle Scholar
  28. Hamann, M., 2003: Enhancing Marine Natural Product Structural Diversity and Bioactivity Through Semisynthesis and Biocatalysis. Curr. Pharm. Des. 9, 879–89.CrossRefGoogle Scholar
  29. Helmholz, H., P. Etoundi, and U. Lindequist, 1999: Cultivation of the Marine Basidiomycete Nia vibrissa (Moore & Meyers). J. Biotechnol. 70, 203–6.CrossRefGoogle Scholar
  30. Helmholz, H, S. Cartellieri, L. He, Thiesen, and B. Niemeyer, 2003: Process Development in Affinity Separation of Glycoconjugates with Lectins as Ligands. J. Chrom. A 1006, 127–35.CrossRefGoogle Scholar
  31. Helmholz, H, C. Ruhnau, C. Schütt, and A. Prange, 2007: Comparative Study on the Cell Toxicity and Enzymatic Activity of Two Northern Scyphozoan Species Cyanea capillata (L.) and Cyanea lamarckii (Peron & Leslueur). Toxicon 50, 53–64.CrossRefGoogle Scholar
  32. Helmholz, H., S. Naatz, S. Lassen, and A. Prange, 2008: Isolation of a cytotoxic glycoprotein from the Scyphozoa Cyanea lamarckii by lectin-affinity chromatography and characterization of molecule interactions by surface plasmon resonance. J. Chromatogr. B 871, 60–6.CrossRefGoogle Scholar
  33. Hinds, M.G., W. Zhang, G. Anderluh, P.E. Hansen, and R.S. Norton, 2002: Solution Structure of the Eukaryotic Pore-Forming Cytolysin Equinatoxin II: Implications for Pore Formation. J. Mol. Biol. 315, 1219–29.CrossRefGoogle Scholar
  34. Ianora, A., M. Boersma, R. Casotti, A. Fontana, J. Harder, F. Hoffmann, H. Pavia, P. Potin, S. Poulet, and G. Toth, 2006: New Trends in Marine Chemical Ecology. Estuar. Coast. 29, 531–51.Google Scholar
  35. Knutsen, G., and K. Hansen, 1997: From Sea to Test: Search for Bioactive Substances from Marine Microalgae and Cyanobacteria. In: Marine Microorganisms for Industry. Eds. Y Le Gal and A Muller-Feuga: IFREMER, France.Google Scholar
  36. König, G.M., and A.D. Wright, 1996: Marine Natural Products Research: Current Directions and Future Potential. Planta Med. 62, 193–211.CrossRefGoogle Scholar
  37. König, G.M., S. Kehraus, S.F. Seibert, A. Abdel-Lateff, and D. Müller, 2006: Natural Products from Marine Organisms and Their Associated Microbes. ChemBioChem 7, 229–38.CrossRefGoogle Scholar
  38. Lanio, M.E., V. Morera, C. Alvarez, M. Tejuca, T. Gomez, F. Pazos, V. Besada, D. Martinez, V. Huerta, G. Padron, and M. de los Angeles Chavez, 2001: Purification and Characterization of Two Hemolysins from Stichodactyla helianthus. Toxicon 39, 187–94.CrossRefGoogle Scholar
  39. Lindequist, U., and T. Schweder, 2001: Marine Biotechnology. Biotechnology 10, 441–84.Google Scholar
  40. Lindl, T., and J. Bauer, 1994: Zell- und Gewebekultur. 3. Auflage ed. Gustav Fischer Verlag, Stuttgart, Jena, New York.Google Scholar
  41. Luckas, B, C. Hummert, and Y Oshima, 2003: Analytical Methods for Paralytic Shellfish Poisons. In: Manual on Harmful Marine Microalgae. Eds. GM Hallegraeff, DM Anderson and AD Cembella: UNESCO Publishing, France.Google Scholar
  42. Macek, P, 1992: Polypeptide Cytolytic Toxins from Sea Anemones (Actiniaria). FEMS Microbiol. Lett. 105, 121–9.CrossRefGoogle Scholar
  43. McConnell, O.J., R.E. Longley, and F.E. Koehn, 1994: The Discovery of Marine Natural Products with Therapeutic Potential. Biotechnol. Ser. 26, 109–74.Google Scholar
  44. Mills, C.E., 2001: Jellyfish Blooms: Are Populations Increasing Globally in Response to Changing Ocean Conditions. Hydrobiologia 451, 55–68.CrossRefGoogle Scholar
  45. Munro, M.H.G., J.W. Blunt, E.J. Dumdei, S.J.H. Hickford, R.E. Lill, S. Li, C.N. Battershill, and A.R. Duckworth, 1999: The Discovery and Development of Marine Compounds with Pharmaceutical Potential. J. Biotechnol. 70, 15–25.CrossRefGoogle Scholar
  46. Nagai, H., 2003: Recent Progress in Jellyfish Toxin Study. J. Health Sci. 49, 337–40.CrossRefGoogle Scholar
  47. Nakamura, K., M. Kitamura, and D. Uemura, 2009: Biologically Active Natural Marine Products. Heterocycles 78, 1–17.CrossRefGoogle Scholar
  48. Olivera, B.M., and L.J. Cruz, 2001: Conotoxins in Retrospect. Toxicon 39, 7–14.CrossRefGoogle Scholar
  49. Papo, N., and S. Yechiel, 2003: Exploring Peptide Membrane Interaction Using Surface Plasmon Resonance: Differentiation Between Pore Formation Versus Membran Disruption by Lytic Peptides. Biochemistry 42, 458–66.CrossRefGoogle Scholar
  50. Parker, M.W., and S.C. Feil, 2005: Pore-Forming Protein Toxins: From Structure to Function. Prog. Biophys. Mol. Biol. 88, 91–142.CrossRefGoogle Scholar
  51. Procksch, P., R.A. Edrada, and R. Ebel, 2003: Drugs from the Sea – Opportunities and Obstacles. Mar. Drugs 1, 5–17.CrossRefGoogle Scholar
  52. Purcell, J.E., and M.N. Arai, 2001: Interaction of Pelagic Cnidarians and Ctenophores with Fish: A Review. Hydrobiologia 451, 27–44.CrossRefGoogle Scholar
  53. Putzier, I., and S. Frings, 2002: Vom Jagdgift zur neuen Schmerztherapie. Biol. Unserer Zeit 32, 148–58.CrossRefGoogle Scholar
  54. Quilliam, M.A., 2003: Chemical Methods for Domoic Acid, the Amnesic Shellfish Poisoning (Asp) Toxin. In: Manual on Harmful Marine Microalgae. Eds. GM Hallegraeff, DM Anderson and AD Cembella: UNESCO Publishing, France.Google Scholar
  55. Riguera, R., 1997: Isolating Bioactive Compounds from Marine Organisms. J. Mar. Biotechnol. 5, 187–93.Google Scholar
  56. Rosenfeld, H, J. Aniulyte, H. Helmholz, J. Liesiene, P. Thiesen, B. Niemeyer, and A. Prange, 2005: Comparison of Modified Supports on the Base of Glycoprotein Interaction Studies and of Adsorption Investigations. J. Chromatogr. A 1092, 76–88.CrossRefGoogle Scholar
  57. Saleem, M., S. Ali, S. Hussain, A. Jabbar, M. Ashrafand, and Y.S. Lee, 2007: Marine Natural Products of Fungal Origin. Nat. Prod. Rep. 24, 1142–52.CrossRefGoogle Scholar
  58. Schulz, B., S. Draeger, T.E. dela Cruz, J. Rheinheimer, K. Siems, S. Loesgen, J. Bitzer, O. Schloerke, A. Zeeck, I. Kock, H. Hussain, J. Dai, and K. Krohn, 2008: Screening Strategies for Obtaining Novel, Biologically Active, Fungal Secondary Metabolites from Marine Habitats. Bot. Mar. 51, 219–34.CrossRefGoogle Scholar
  59. Scudiero, D.A., R.H. Shoemaker, K.D. Paull, A. Moaks, S. Tierny, T.H. Nofziger, M.J. Currens, D. Seniff, and M.R. Boyd, 1988: Evaluation of a Soluble Tetrazolium/Formazan Assay for Cell Growth and Drug Sensitivity in Culture Using Human and Other Tumor Cell Lines. Cancer Res. 48, 4827–33.Google Scholar
  60. Sipkema, D., R. Osinga, W. Schatton, D. Mendola, J. Tramper, and R.H. Wijffels, 2005: Large-Scale Production of Pharmaceuticals by Marine Sponges: Sea, Cell, or Synthesis? Biotechnol. Bioeng. 90, 201–22.CrossRefGoogle Scholar
  61. Sponga, F., L. Cavaletti, A. Lazzarini, A. Borghi, I. Ciciliato, D. Losi, and F. Marinelli, 1999: Biodiversity and Potentials of Marine-Derived Microorganisms. J. Biotechnol. 70, 65–9.CrossRefGoogle Scholar
  62. Suput, D., R. Fangez, and M. Bunc; 2001: Cardiovascular Effects of Equinatoxin III from Sea Anemone Actinia equina (L.). Toxicon 39, 1421–7.CrossRefGoogle Scholar
  63. Thedinga, E., A. Ullrich, S. Drechsel, R. Niendorf, A. Kob, D. Runge, A. Keuer, I. Freund, M. Lehmann, and R. Ehret, 2007: In Vitro System for the Prediction of Hepatotoxic Effects in Primary Hepatocytes. ALTEX 1, 22–34.Google Scholar
  64. Turk, T, 1991: Cytolytic Toxins from Sea Anemones. J. Toxicol. Toxin Rev. 10, 223–62.CrossRefGoogle Scholar
  65. van der Wielen, L.A.M., and L.K. Cabatingan, 1999: Fishing Products from the Sea – Rational Downstream Processing of Marine Bioproducts. J. Biotechnol. 70, 363–71.CrossRefGoogle Scholar
  66. Vanhoye, D, F. Bruston, S. Al-Amri, A. Ladram, M. Amiche, and P. Nicolas: Membrane Association, Electrostatic Sequestration, and Cytotoxicity of Gly-Leu Rich Peptide Orthologs with Different Functions. Biochemistry 43, 8391–409.CrossRefGoogle Scholar
  67. Vetter, W., 2002: Lipophilic and Bioaccumulating Natural Halogenated Products in the Marine Environment. Speciality Chem. Mag. 22, 30–3.Google Scholar
  68. Vetter, W., 2006: Marine Halogenated Natural Products of Environmental Relevance. Rev. Environ. Contam. Toxicol. 188, 1–57.CrossRefGoogle Scholar
  69. Vetter, W., N. Rosenfelder, S. Kraan, and J. Hiebl, 2008: Structure and Origin of the Natural Halogenated Monoterpene MHC-1 and Its Concentrations in Marine Mammals and Fish. Chemosphere 73, 7–13.CrossRefGoogle Scholar
  70. Yasumoto, T., and M. Satake, 1998: Bioactive Compounds from Marine Microalgae. Chimia 52, 63–8.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Helmholtz-Zentrum Geesthacht, Marine Bioanalytic Chemistry (KOC)Institute of Coastal ResearchGeesthachtGermany

Personalised recommendations