An overview on the origin and production of tetrodotoxin, a potent neurotoxin

Tetrodotoxin (TTX) is a deadly neurotoxin which selectively inhibits Na+ activation mechanism of nerve impulse, without affecting the permeability of K+ ions. Because of this sodium channel blocking action, it is majorly being studied for biomedical applications. TTX is present in taxonomically diverse groups of animals inhabiting terrestrial, marine, fresh water and brackish water environments, still its origin remains unclear. The extensive study of the toxin has revealed a few possibilities of its origin. This review reports on the aspects of the origin of TTX, where the primary focus is on its exogenous origin. The significance of bacterial, cellular and environmental factors in its biogenesis and accumulation is also discussed. The possible facets for engineering the bacterial genomics to modulate the gene expression for TTX production are also outlined.

[1]  S. Cary,et al.  Investigating Diet as the Source ofTetrodotoxin in Pleurobranchaea maculata , 2013, Marine drugs.

[2]  Xiao‐Ming Li,et al.  Secondary Metabolites from Penicillium pinophilum SD-272, a Marine Sediment-Derived Fungus , 2013, Marine drugs.

[3]  Martha B. Arnaud,et al.  Comprehensive annotation of secondary metabolite biosynthetic genes and gene clusters of Aspergillus nidulans, A. fumigatus, A. niger and A. oryzae , 2013, BMC Microbiology.

[4]  Nobuyuki Fujita,et al.  DoBISCUIT: a database of secondary metabolite biosynthetic gene clusters , 2012, Nucleic Acids Res..

[5]  E. Moczydlowski The molecular mystique of tetrodotoxin. , 2012, Toxicon : official journal of the International Society on Toxinology.

[6]  T. Noguchi,et al.  Instrumental Analysis of Tetrodotoxin , 2012 .

[7]  L. Botana,et al.  New Gastropod Vectors and Tetrodotoxin Potential Expansion in Temperate Waters of the Atlantic Ocean , 2012, Marine drugs.

[8]  T. Yasumoto,et al.  Isolation and Structural Determination of the First 8-epi-type Tetrodotoxin Analogs from the Newt, Cynops ensicauda popei, and Comparison of Tetrodotoxin Analogs Profiles of This Newt and the Puffer Fish, Fugu poecilonotus , 2012, Marine drugs.

[9]  A. Kurz,et al.  Variability of tetrodotoxin and of its analogues in the red-spotted newt, Notophthalmus viridescens (Amphibia: Urodela: Salamandridae). , 2012, Toxicon : official journal of the International Society on Toxinology.

[10]  P. Yu,et al.  Isolation and Identification of a New Tetrodotoxin-Producing Bacterial Species, Raoultella terrigena, from Hong Kong Marine Puffer Fish Takifugu niphobles , 2011, Marine drugs.

[11]  L. Gram,et al.  Production of Bioactive Secondary Metabolites by Marine Vibrionaceae , 2011, Marine drugs.

[12]  Chang-li Lu,et al.  Tetrodotoxin alleviates acute heroin withdrawal syndrome: A multicentre, randomized, double‐blind, placebo‐controlled study , 2011, Clinical and experimental pharmacology & physiology.

[13]  J. Kalaitzis,et al.  On the origins and biosynthesis of tetrodotoxin. , 2011, Aquatic toxicology.

[14]  R. Pettit Culturability and Secondary Metabolite Diversity of Extreme Microbes: Expanding Contribution of Deep Sea and Deep-Sea Vent Microbes to Natural Product Discovery , 2011, Marine Biotechnology.

[15]  Jun Wang,et al.  Isolation of a Lysinibacillus fusiformis strain with tetrodotoxin-producing ability from puffer fish Fugu obscurus and the characterization of this strain. , 2010, Toxicon : official journal of the International Society on Toxinology.

[16]  Jilin Xu,et al.  A novel TTX-producing Aeromonas isolated from the ovary of Takifugu obscurus. , 2010, Toxicon : official journal of the International Society on Toxinology.

[17]  C. Hanifin The Chemical and Evolutionary Ecology of Tetrodotoxin (TTX) Toxicity in Terrestrial Vertebrates , 2010, Marine drugs.

[18]  Jun Wang,et al.  Isolation and characterization of a Bacillus species capable of producing tetrodotoxin from the puffer fish Fugu obscurus , 2010 .

[19]  S. Taniyama,et al.  Toxins of Pufferfish That Cause Human Intoxications , 2010 .

[20]  D. Anderson,et al.  Origin of Saxitoxin Biosynthetic Genes in Cyanobacteria , 2009, PloS one.

[21]  C. Hertweck,et al.  Triggering cryptic natural product biosynthesis in microorganisms. , 2009, Organic & biomolecular chemistry.

[22]  Xuan Luo,et al.  Toxin-screening and identification of bacteria isolated from highly toxic marine gastropod Nassarius semiplicatus. , 2008, Toxicon : official journal of the International Society on Toxinology.

[23]  T. Narahashi Tetrodotoxin —A brief history— , 2008, Proceedings of the Japan Academy. Series B, Physical and biological sciences.

[24]  T. Noguchi,et al.  Tetrodotoxin – Distribution and Accumulation in Aquatic Organisms, and Cases of Human Intoxication , 2008, Marine drugs.

[25]  Chun-fai Yu,et al.  Occurrence of paralytic shellfish toxins in Cambodian Mekong pufferfish Tetraodon turgidus: selective toxin accumulation in the skin. , 2008, Toxicon : official journal of the International Society on Toxinology.

[26]  N. Keller,et al.  Regulation of secondary metabolite production in filamentous ascomycetes. , 2008, Mycological research.

[27]  M. Yotsu-Yamashita,et al.  6,11-Dideoxytetrodotoxin from the puffer fish, Fugu pardalis. , 2007, Toxicon : official journal of the International Society on Toxinology.

[28]  G. Boxshall,et al.  Isolation and characterization of bacteria from the copepod Pseudocaligus fugu ectoparasitic on the panther puffer Takifugu pardalis with the emphasis on TTX. , 2007, Toxicon : official journal of the International Society on Toxinology.

[29]  Yamamori,et al.  Production of Tetrodotoxin by the Intestinal Bacteria of a Puffer Fish Takifugu niphobles*1 , 2007 .

[30]  Masato,et al.  Vibrio alginolyticus, a TTX-producing Bacterium Isolated from the Starfish Astropecten polyacanthus , 2007 .

[31]  C. Watanabe,et al.  Pyocyanin isolated from a marine microbial population: synergistic production between two distinct bacterial species and mode of action. , 2006, Chemistry & biology.

[32]  T. Noguchi,et al.  Toxicity of pufferfish Takifugu rubripes cultured in netcages at sea or aquaria on land. , 2006, Comparative biochemistry and physiology. Part D, Genomics & proteomics.

[33]  S. Warber,et al.  Plant Biotechnology for the Production of Natural Products , 2006 .

[34]  P. Yu,et al.  Detection of Tetrodotoxin and Bacterial Production by Serratia Marcescens , 2005 .

[35]  Zhenlong Wu,et al.  Toxicity and distribution of tetrodotoxin-producing bacteria in puffer fish Fugu rubripes collected from the Bohai Sea of China. , 2005, Toxicon : official journal of the International Society on Toxinology.

[36]  Jinfang Zhang,et al.  A new tetrodotoxin-producing actinomycete, Nocardiopsis dassonvillei, isolated from the ovaries of puffer fish Fugu rubripes. , 2005, Toxicon : official journal of the International Society on Toxinology.

[37]  J. Duus,et al.  Medium dependant production of corymbiferone a novel product from Penicillium hordei cultured on plant tissue agar , 2005 .

[38]  E. Brodie,et al.  Secretion and regeneration of tetrodotoxin in the rough-skin newt (Taricha granulosa). , 2004, Toxicon : official journal of the International Society on Toxinology.

[39]  P. Yu,et al.  Two novel species of tetrodotoxin-producing bacteria isolated from toxic marine puffer fishes. , 2004, Toxicon : official journal of the International Society on Toxinology.

[40]  J. Lorén,et al.  Aeromonas molluscorum sp. nov., isolated from bivalve molluscs. , 2004, International journal of systematic and evolutionary microbiology.

[41]  E. Brodie,et al.  No evidence for an endosymbiotic bacterial origin of tetrodotoxin in the newt Taricha granulosa. , 2004, Toxicon : official journal of the International Society on Toxinology.

[42]  C. Hanifin,et al.  A predictive model to estimate total skin tetrodotoxin in the newt Taricha granulosa. , 2004, Toxicon : official journal of the International Society on Toxinology.

[43]  S. Taniyama,et al.  Occurrence of saxitoxins as a major toxin in the ovary of a marine puffer Arothron firmamentum. , 2004, Toxicon : official journal of the International Society on Toxinology.

[44]  Stuart Carroll,et al.  The production of tetrodotoxin-like substances by nemertean worms in conjunction with bacteria , 2003 .

[45]  E. Brodie,et al.  Tetrodotoxin levels of the rough-skin newt, Taricha granulosa, increase in long-term captivity. , 2002, Toxicon : official journal of the International Society on Toxinology.

[46]  T. Noguchi,et al.  Secretory glands of tetrodotoxin in the skin of the Japanese newt Cynops pyrrhogaster. , 2002, Toxicon : official journal of the International Society on Toxinology.

[47]  S. Horinouchi,et al.  A microbial hormone, A-factor, as a master switch for morphological differentiation and secondary metabolism in Streptomyces griseus. , 2002, Frontiers in bioscience : a journal and virtual library.

[48]  T. Noguchi,et al.  Toxicity and toxin profiles of the newt, Cynops pyrrhogaster from western Japan. , 2001, Journal of natural toxins.

[49]  Y Ueno,et al.  The voltage-sensitive sodium channel is a bell-shaped molecule with several cavities , 2001, Nature.

[50]  T. Narahashi PHARMACOLOGY OF TETRODOTOXIN , 2001 .

[51]  S. Sato,et al.  Frequent occurrence of paralytic shellfish poisoning toxins as dominant toxins in marine puffer from tropical water. , 2000, Toxicon : official journal of the International Society on Toxinology.

[52]  Cheorl-Ho Kim,et al.  A Tetrodotoxin-Producing Vibrio Strain, LM-1, from the Puffer Fish Fugu vermicularis radiatus , 2000, Applied and Environmental Microbiology.

[53]  I. Nagelkerken,et al.  Environmental microbiology: A tetrodotoxin-producing marine pathogen , 2000, Nature.

[54]  J. Duncan,et al.  Experimental use of tetrodotoxin for corneal pain after excimer laser keratectomy. , 1998, Cornea.

[55]  J. Daly,et al.  Absence of tetrodotoxins in a captive-raised riparian frog, Atelopus varius. , 1997, Toxicon : official journal of the International Society on Toxinology.

[56]  S. Sato,et al.  Saxitoxin as a toxic principle of a freshwater puffer, Tetraodon fangi, in Thailand. , 1997, Toxicon : official journal of the International Society on Toxinology.

[57]  T. Noguchi,et al.  Microflora and tetrodotoxin-producing bacteria in a gastropod, Niotha clathrata. , 1995, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[58]  T. Yue,et al.  Neuroprotective Effects of Tetrodotoxin as a Na+ Channel Modulator and Glutamate Release Inhibitor in Cultured Rat Cerebellar Neurons and in Gerbil Global Brain Ischemia , 1994, Stroke.

[59]  T. Noguchi,et al.  Microflora and Tetrodotoxin-producing Bacteria in the Lined Moon Shell Natica lineata. , 1994 .

[60]  K. Kogure,et al.  Presence of Tetrodotoxin and Tetrodotoxin-Producing Bacteria in Freshwater Sediments , 1993, Applied and environmental microbiology.

[61]  T. Birkbeck,et al.  Effect of Phosphate Concentration on Production of Tetrodotoxin by Alteromonas tetraodonis , 1993, Applied and environmental microbiology.

[62]  K. Kogure,et al.  Tetrodotoxin production of actinomycetes isolated from marine sediment , 1991 .

[63]  K. Limpakarnjanarat,et al.  Toxicity of the freshwater puffer fish Tetraodon fangi and T. palembangensis from Thailand. , 1991, Toxicon : official journal of the International Society on Toxinology.

[64]  T. Yasumoto,et al.  Taxonomy of four marine bacterial strains that produce tetrodotoxin. , 1990, International journal of systematic bacteriology.

[65]  K. Kogure,et al.  Identification of Deep-Sea-Sediment Bacteria Which Produce Tetrodotoxin , 1990, Applied and environmental microbiology.

[66]  S. Watabe,et al.  New Aspects of Tetrodotoxin , 1990 .

[67]  E. V. Thuesen,et al.  Bacterial Production of Tetrodotoxin in Four Species of Chaetognatha , 1989 .

[68]  T. Noguchi,et al.  Tetrodotoxin-producing bacteria from the blue-ringed octopus Octopus maculosus , 1989 .

[69]  T. Matsui,et al.  Studies on the toxification of puffer fish - I. Production to tetrodotoxin by the intestinal bacteria of a puffer fish Takifugu niphobles. , 1989 .

[70]  T. Noguchi Food chain-associated toxification of tetrodotoxin-bearing animals , 1988 .

[71]  T. Noguchi,et al.  Tetrodotoxin-producing bacteria from the horseshoe crab Carcinoscorpius rotundicauda. , 1988 .

[72]  E. V. Thuesen,et al.  Accumulation of tetrodotoxin in marine sediment , 1988 .

[73]  H. Sugita,et al.  Vibrio alginolyticus, a tetrodotoxin-producing bacterium, in the intestines of the fish Fugu vermicularis vermicularis , 1987 .

[74]  T. Noguchi,et al.  Marine bacteria which produce tetrodotoxin , 1987, Applied and environmental microbiology.

[75]  憲永 三輪,et al.  トゲモミジガイ(ヒトデ)から分離したVibrio alginolyticusによるテトロドトキシンの産生 , 1987 .

[76]  H. Sugita,et al.  Identification of a Tetrodotoxin-producing Bacterium Isolated from the Xanthid Crab Atergatis floridus , 1987 .

[77]  H. Naoki,et al.  Production of tetrodotoxin and its derivatives by Pseudomonas sp. isolated from the skin of a pufferfish. , 1987, Toxicon : official journal of the International Society on Toxinology.

[78]  Y. Kotaki,et al.  Bacterial Production of Tetrodotoxin and Anhydrotetrodotoxin , 1986 .

[79]  H. Sugita,et al.  Occurrence of tetrodotoxin and anhydrotetrodotoxin in Vibrio sp. isolated from the intestines of a xanthid crab, Atergatis floridus. , 1986, Journal of biochemistry.

[80]  T. Noguchi,et al.  Tetrodotoxin as a biological defense agent for puffers [Fugu niphobles, F. vermicularis vermicularis and F. pardalis] , 1985 .

[81]  H. Mosher,et al.  Occurrence and Origin of Tetrodotoxin , 1984 .

[82]  玉雄 野口,et al.  ボウシュウボラの毒化機構-トゲモミジAstropecten polyacanthusにおけるテトロドトキシンの検出 , 1982 .

[83]  T. Matsui,et al.  Difference in accumulation of puffer fish toxin and crystalline tetrodotoxin in the puffer fish,Fugu rubripes rubripes. , 1981 .

[84]  T. Narahashi,et al.  Stabilization and rectification of muscle fiber membrane by tetrodotoxin. , 1960, The American journal of physiology.