Toxins Produced by Marine Microorganisms: A Short Review

  • Valentin A. StonikEmail author
  • Inna V. Stonik
Reference work entry
Part of the Toxinology book series (TOXI)


Structures, toxicological properties, and mechanisms of biological action of the best known representatives of the main groups of marine microbial toxins are presented. It is shown that many compounds have complex chemical structures and possess extremely high toxicities. These highly dangerous toxins are accumulated in mollusks and other kinds of sea food. They represent a serious health and ecological problem.


Okadaic Acid Domoic Acid Paralytic Shellfish Poisoning Minke Whale Marine Cyanobacterium 
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. Aligizaki K, Katikou P, Milandri A, Diogene J. Occurence of palytoxin-group toxins in seafood and future strategies to complement the present state of the art. Toxicon. 2011;57:390–9.CrossRefPubMedGoogle Scholar
  2. Allingham J, Miles C, Rayment I. A structural basis for regulation of actin polymerization by pectenotoxins. J Mol Biol. 2007;371:959–70.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Amzil Z, Sibat M, Chomerat N, Grossel H, Marco-Miralles F, Lemee R, Nezan E, Sechet V. Ovatoxin-a and palytoxin accumulation in seafood in relation to Ostreopsis cf. ovata blooms on the French Mediterranean coast. Mar Drugs. 2012;10:477–96.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Araos R, Molgo J, de Marsac N. Neurotoxic cyanobacterial toxins. Toxicon. 2010;56:813–28.CrossRefGoogle Scholar
  5. Araoz R, Servent D, Molgo J, Iorga B, Fruchart-Gaillard C, Benoit E, Gu Z, Stivala C, Zakarian A. Total synthesis of pinnatoxins A and G and revision of the mode of action of pinnatoxin A. J Am Chem Soc. 2011;133(27):10499–511.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Armstrong J, Beau S, Cheon W, Christ H, Fujioka W, Ham L, Hawkins H, Jin S, Kang Y, Kishi M, Martinelli W, McWhorter M, Mizuno M, Nakata M, Stutz A, Talamas F, Taniguchi M, Tino J, Ueda K, Uenishi J, White J, Yonaga M. Total synthesis of palytoxin carboxylic-acid and palytoxin amide. J Am Chem Soc. 1989;111(19):7530–3.CrossRefGoogle Scholar
  7. Asakawa M, Katsutoshi I, Kajihara H. Highly toxic ribbon worm Cephalothrix simula containing tetrodotoxin in Hiroshima Bay, Hiroshima Prefecture, Japan. Toxins. 2013;5(2):376–95.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Aune T, Aasen J, Miles C, Larsen S. Effect of mouse strain and gender on LD(50) of yessotoxin. Toxicon. 2008;52:535–40.CrossRefPubMedGoogle Scholar
  9. Cha J, Christ W, Finan J, Fujioka H, Kishi Y, Klein L, Ko S, Leder J, McWhorter W, Pfaff K-P, Yonaga M. Stereochemistry of Palytoxin. 4. Compete structure. J Am Chem Soc. 1982;104(25):7369–71.Google Scholar
  10. Chau R, Kalaitzis J, Neilan B. On the origins and biosynthesis of tetrodotoxin. Aquat Toxicol. 2011;104(1–2):61–72.CrossRefPubMedGoogle Scholar
  11. Daranas A, Norte M, Fernandez J. Review. Toxic marine microalgae. Toxicon. 2001;39:1101–32.CrossRefPubMedGoogle Scholar
  12. Dominguez H, Paz B, Daranos A, Norte M, Franco J, Fernandez J. Dinoflagellate polyether within the yessoetoxin, pectenotoxin and okadaic axid toxin groups: characterization, analysis and human health implications. Toxicon. 2010;56(2):191–217.CrossRefPubMedGoogle Scholar
  13. Dounay A, Forsyth C. Okadaic acid: the archetypal serine/threonine protein phosphatase inhibitor. J Curr Med Chem. 2002;9:1939–80.CrossRefGoogle Scholar
  14. Edwards D, Marquez B, Nogle L, McPhail K, Goeger D, Roberts M, Gerwick W. Structure and biosynthesis of the jamaicamides, new mixed polyketide-peptideneurotoxins from the marine cyanobacterium Lyngbya majuscula. Chem Biol. 2004;11(6):817–33.CrossRefPubMedGoogle Scholar
  15. Espina B, Rubiolo J. Marine toxins and the cytoskeleton: pectenotoxins, unusual macrolides that disrupt actin. FEBS J. 2008;275:6082–8.CrossRefPubMedGoogle Scholar
  16. Fire S, Wang Z, Berman M, Langlois G, Morton S, Sekila-Wood E, Benites-Nelson C. Trofic transfer of the harmful algal toxin domoic acid as a cause of death in a Minke whale (Balaenoptera acutorostrata) stranding in Southern California. Aquat Mamm. 2010;36(4):342–50.CrossRefGoogle Scholar
  17. Fozzard H, Lipkind G. The tetrodotoxin binding site is within the outer vestibule of the sodium channel. Mar Drugs. 2010;8:219–34.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Frew R, Wang Y, Weiss T, Nelson P, Sawyer T. Attenuation of maitotoxin-induced cytotoxicity in rat aortic smooth muscle cells by inhibitors of Na+/Ca2+ exchange, and calpain activation. Toxicon. 2008;51(8):1400–8.CrossRefPubMedGoogle Scholar
  19. Garibo D, de la Iglesia P, Diogene J, Campas M. Inhibition equivalency factors for dinophysistoxin-1 and dinophysistoxin-2 in protein phosphatase assays: applicability to the analysis of shellfish samples and comparison with LC-MS/MS. J Agric Food Chem. 2013;61(10):2572–9.CrossRefPubMedGoogle Scholar
  20. Halstead BW, Courville DA. Poisonous and Venomous Marine Animals of the World, 1967;2:784–844, US Govern. Pinting Office, Washington.Google Scholar
  21. Hamilton B, Whittle N, Shaw G, Eaglesham G, Moore M, Lewis R. Human fatality associated with Pacific ciguatoxin contaminated fish. Toxicon. 2010;56:668–73.CrossRefPubMedGoogle Scholar
  22. Inuzuka T, Uemura D, Arimoto H. The conformational features of palytoxin in aqueous solution. Tetrahedron. 2008;64:7718–23.CrossRefGoogle Scholar
  23. Ito E, Satake M, Yasumoto T. Pathological effects of lyngbyatoxin A upon mice. Toxicon. 2002;40(5):551–6.CrossRefPubMedGoogle Scholar
  24. James K, Moroney C, Roden C, Satake M, Yasumoto T, Lehane M, Furey A. Azaspiracid, a new marine toxin having unique spiro ring assemblies, isolated from Irish mussels, Mytilus edulis. Toxicon. 2003;41:145–51.CrossRefPubMedGoogle Scholar
  25. Kishi Y. Complete structure of maitotoxin. Pure Appl Chem. 1998;70(2):339–44.CrossRefGoogle Scholar
  26. Kita M, Uemura D. Iminium alkaloids from marine invertebrates: structure, biological activity, and biogenesis. Chem Lett. 2005;34(4):454–9.CrossRefGoogle Scholar
  27. Kita M, Uemura D. Marine huge molecules: the longest carbon chains in natural products. Chem Rec. 2010;10(1):48–52.CrossRefPubMedGoogle Scholar
  28. Kobayashi K, Takata Y, Kodama M. Direct contact between Pseudo-nitzchia multiseries and bacteria is necessary for the diatom to produce a high level of domoic acid. Fish Sci. 2009;75(3):771–6.CrossRefGoogle Scholar
  29. Kodama M, Ogata T, Sakamoto S, Sato S, Honda T, Miwatani T. Production of paralytic shellfish toxins by a bacterium Moraxella sp isolated from Protogonyaulax tamarense. Toxicon. 1990;28:707–14.CrossRefPubMedGoogle Scholar
  30. Larsen K, Petersen D, Wilkins A, Samdal I, Sandvik M, Rundberget T, Goldstone D, Arcus V, Hovgaard P, Rise F, Rehmann N, Hess P, Miles C. Clarification of the C-35 stereochemistries of dinophysistoxin-1 and dinophysistoxin-2 and its consequences for binding to protein phosphatase. Chem Res Toxicol. 2007;20:868–75.CrossRefPubMedGoogle Scholar
  31. Leira F, Cabado A, Vieytes M, Roman Y, Alfonso A, Botana L, Yasumoto T, Malaguti T, Rossini G. Characterization of F-actin depolymerization as a major toxic event induced by pectenotoxin-6 in neuroblastoma cells. Biochem Pharmacol. 2002;63:1979–88.CrossRefPubMedGoogle Scholar
  32. LePage K, Goeger D, Yokokawa F, Asano T, Shioiri T, Gerwick W, Murray T. The neurotoxic lipopetide kalkitoxin interacts with voltage-sensitive sodium channels in cerebellar granule neurons. Toxicol Lett. 2005;158:133–9.CrossRefPubMedGoogle Scholar
  33. Lewis R, Sellin M, Poli M, Norton R, McLeod J, Sheil M. Purification and characterization of ciguatoxins from moray eel (Lycodontis javanicus, Muraenidae). Toxicon. 1991;29:1115–27.CrossRefPubMedGoogle Scholar
  34. McMahon T, Silke J. West coast of Ireland winter toxicity of unknown etiology in m ussels. Harmful Algae News. 1996;14:2.Google Scholar
  35. Miyazawa K, Noguchi T. Distribution and origin of tetrodotoxin. J Toxicol Toxin Rev. 2001;20:11–33.CrossRefGoogle Scholar
  36. Moloney M. Excitory amino acids. Nat Prod Rep. 1998;15(2):205–19.CrossRefPubMedGoogle Scholar
  37. Moore R, Bartolini G. Structure of palytoxin. J Am Chem Soc. 1981;103:2491–4.CrossRefGoogle Scholar
  38. Moore R, Scheuer P. Palytoxin: a new marine toxin from a coelenterate. Science. 1971;172:495–8.CrossRefPubMedGoogle Scholar
  39. Munday R. Palytoxin toxicology: animals studies. Toxicon. 2011;57:470–7.CrossRefPubMedGoogle Scholar
  40. Murata M, Naoki H, Matsunaga S, Satake M, Yasumoto T. Structure and partial stereochemical assignments for maitotoxin, the most toxic and largest natural non-biopolymer. J Am Chem Soc. 1996;116:7098–107.CrossRefGoogle Scholar
  41. Nakanishi K. The chemistry of brevetoxins: a review. Toxicon. 1985;23:473–9.CrossRefPubMedGoogle Scholar
  42. Narahashi T. Pharmacology of tetrodotoxin. J Toxicol Toxin Rev. 2001;20:67–84.CrossRefGoogle Scholar
  43. Nicholson G, Lewis R. Ciguatoxins: cyclic polyether modulators of voltage-gated ion channel function. Mar Drugs. 2006;4:82–118.CrossRefPubMedCentralGoogle Scholar
  44. Nicolaou K, Koftis T, Vyskocil S, Petrovic G, Tang W, Frederick M, Chen D, Li Y, Ling T, Yamada Y. Total synthesis and structural elucidation of azaspiracid-1. Final assignment and total synthesis of the correct structure of azaspiracid-1. J Am Chem Soc. 2006;128:2859–72.CrossRefPubMedGoogle Scholar
  45. Nicolaou K, Aversa R, Jin J, Rivas F. Synthesis of the ABCDEFG ring system of maitotoxin. J Am Chem Soc. 2010;132(19):6855–61.CrossRefPubMedPubMedCentralGoogle Scholar
  46. Nicolaou K, Baker T, Nakamura T. Synthesis of the WXYZA’ domain of maitotoxin. J Am Chem Soc. 2011a;133(2):220–6.CrossRefPubMedPubMedCentralGoogle Scholar
  47. Nicolaou K, Seo J, Nakamura T, Aversa R. Synthesis of the C’, D’, E’, F’ domain of maitotoxin. J Am Chem Soc. 2011b;133(2):214–9.CrossRefPubMedPubMedCentralGoogle Scholar
  48. Nieto F, Cobos E, Tejada M, Sanches-Fernandes C, Gonzales-Cano R, Cendan C. Tetrodotoxin (TTX) as a therapeutic agent for pain. Mar Drugs. 2012;10:281–305.CrossRefPubMedPubMedCentralGoogle Scholar
  49. Noguchi T, Arakawa O. Tetrodotoxin – distribution and accumulation in aquatic organisms, and cases of human intoxication. Mar Drugs. 2008;6:220–42.CrossRefPubMedPubMedCentralGoogle Scholar
  50. Nonomura T, Sasaki M, Matsumori N, Murata M, Tachibana K, Yasumoto T. The complete structure of maitoxin, part 11: configuration of the C135–C142 side chain and absolute configuration of the entire molecule. Angew Chem Int Ed. 1996;35:1675–8.CrossRefGoogle Scholar
  51. Onyabu N, Nishikawa T, Isobe M. First asymmetric total synthesis of tetrodotoxin. J Am Chem Soc. 2003;125(29):8798–805.CrossRefGoogle Scholar
  52. Paz B, Daranas A, Norte M, Riobo P, Franco J, Fernandez J. Yessotoxins, a group of marine polyether toxins: an overview. Mar Drugs. 2008;6:73–102.CrossRefPubMedPubMedCentralGoogle Scholar
  53. Piel J. Metabolites from symbiotic bacteria. Nat Prod Rep. 2004;21:519–38.CrossRefPubMedGoogle Scholar
  54. Pulido O. Domoic acid toxicologic pathology: a review. Mar Drugs. 2008;6:180–219.CrossRefPubMedPubMedCentralGoogle Scholar
  55. Reguera B, Velo-Suarez L, Raine R, Park M. Harmful Dinophysis species: a review. Harmful Algae. 2012;14:87–106.CrossRefGoogle Scholar
  56. Rossini G, Bigiani A. Palytoxin action on the Na+, K+-ATPase and the disruption of ion equilibria in biological systems. Toxicon. 2011;57:429–39.CrossRefPubMedGoogle Scholar
  57. Russell F, Egen N. Ciguateric fishes, ciguatoxin (CTX) and ciguatera poisoning. J Toxicol Toxin Rev. 1991;10:37–62.CrossRefGoogle Scholar
  58. Satake M, Terasawa K, Kadowaki Y, Yasumoto T. Relative configuration of yessotoxin and isolation of two new analogs from toxic scallops. Tetrahedron Lett. 1996;37:5955–8.CrossRefGoogle Scholar
  59. Shimizu Y. Microaglal metabolites: a new perspective. Annu Rev Microbiol. 1996;50:431–65.CrossRefPubMedGoogle Scholar
  60. Skov J, Lundholm N, Moestrup O, Larsen J. In: Lindley J, editor. Potentially toxic phytoplankton. 4. The diatom genus Pseudo-nitzschia (Diatomophyceae/Bacillariophyceae. ICES identification leaflets for plankton, vol. 185. Copenhagen: ICES; 1999. p. 1–23.Google Scholar
  61. Stonik V, Stonik I. Investigations of marine toxins: chemical and biological aspects. Russ Chem Rev. 2010;79(5):397–419.CrossRefGoogle Scholar
  62. Suehiro M. Historical review on chemical and medical studies of globefish toxins before World War II in Japanese. Jpn. Soc History Pharmacy. 1994;29:428–434.Google Scholar
  63. Tachibana K, Scheuer P, Tsukatani Y, Kikuchi H, Van Engen D, Clardy J, Gopichand Y, Schmitz F. Okadaic acid, a cytotoxic polyether from two marine sponges of the genus Halichondria. J Am Chem Soc. 1981;103(9):2469–71.CrossRefGoogle Scholar
  64. Takeuchi A, Reyes N, Artigas P, Gadsby D. The ion pathway through the opened Na+, K+-ATPase pump. Nature. 2008;456(7220):413–6.CrossRefPubMedPubMedCentralGoogle Scholar
  65. Tillmann U, Elbrachter M, Krock B, John U, Cembella A. Azadinium spinosum gen. et sp. nov. (Dinophyceae) identified as a primary producer of azaspiracid toxins. Eur J Phycol. 2009;44:63–79.CrossRefGoogle Scholar
  66. Todd E. Domoic acid and amnesic shellfish poisoning: a review. J Food Prot. 1993;56(1):69–83.Google Scholar
  67. Twiner M, Rehmann N, Hess P, Doucette G. Azaspiracid shellfish poisoning: a review on the ecology, chemistry, toxicology and human health impacts. Mar Drugs (Special issue on Marine Toxins). 2008;6:39–72.Google Scholar
  68. Twiner M, Doucette G, Rasky A, Xyang X, Roth B, Sanguinetti M. Marine algal toxin azaspiracid is an open-state blocker of hERG potassium channels. Chem Res Toxicol. 2012;25(9):1975–84.CrossRefPubMedPubMedCentralGoogle Scholar
  69. Uemura D, Chou T, Haino T, Nagatsu A, Fukuzawa S, Zheng S, Chen H. Pinnatoxin-A – a toxic amphoteric macrocycle from the okinawan bivalve Pinna muricata. J Am Chem Soc. 1995;117(3):1155–6.CrossRefGoogle Scholar
  70. Usami M, Satake M, Ishida S, Inoue A, Yukiko K, Yasumoto T. Palytoxin analogs from the dinoflagellate Ostreopsis siamensis. J Am Chem Soc. 1995;117:5389–90.CrossRefGoogle Scholar
  71. Vetter I, Touska F, Hess A, Hinsbey R, Salter S, Lampert A, Sergejeva M, Sharov A, Collins L, Eberhardt M, Engel M, Cabot P, Wood J, Vlachova V, Reeh P, Lewis R, Zimmermann K. Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling. EMBO J. 2012;31(19):3795–808.CrossRefPubMedPubMedCentralGoogle Scholar
  72. Wang D. Neurotoxins from marine dinoflagellates: a brief review. Mar Drugs. 2008;6:349–71.CrossRefPubMedPubMedCentralGoogle Scholar
  73. Watkins S, Reich A, Fleming L, Hammond R. Neurotoxic shellfish poisoning. Mar Drugs. 2008;6(3):431–55.CrossRefPubMedPubMedCentralGoogle Scholar
  74. White JD, Xu Q, Lee CS, Valeriote FA. Total synthesis and biological evaluation of (+)-kalkitoxin, a cytotoxic metabolite of the cyanobacterium Lyngbya majuscula. Org Biomol Chem. 2004;2:2092–102.CrossRefPubMedGoogle Scholar
  75. Woodward RB. The structure of tetrodotoxin. Pure Appl. Chem. 1964;9:49–74Google Scholar
  76. Yasumoto T, Murata M. Marine toxins. Chem Rev. 1993;93:1897–909.CrossRefGoogle Scholar
  77. Yasumoto T, Seino N, Murakami Y, Murata M. Toxin produced by benthic dinoflagellates. Biol Bull. 1987;172:128–31.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.G.B. Elyakov Pacific Institute of Bioorganic ChemistryFar Eastern Branch of the Russian Academy of SciencesVladivostokRussia
  2. 2.A.V. Zhirmunsky Institute of Marine BiologyFar-Eastern Branch of the Russian Academy of SciencesVladivostokRussia

Personalised recommendations