Lyngbyatoxin-a explained

Lyngbyatoxin-a is a cyanotoxin produced by certain cyanobacteria species, most notably Moorea producens (formerly Lyngbya majuscula). It is produced as defense mechanism to ward off any would-be predators of the bacterium, being a potent blister agent as well as carcinogen. Low concentrations cause a common skin condition known as seaweed dermatitis.[1] [2] [3] [4] [5] [6]

Biosynthesis

Lyngbyatoxin is a terpenoid indole alkaloid that belongs to the class of non-ribosomal peptides (NRP).[7] Lyngbyatoxin contains a nucleophilic indole ring that takes part in the activation of protein kinases. Figure 1, shows the biosynthesis of Lyngbyatoxin reported by Neilan et al. and Gerwick et al. The non-ribosomal peptide synthase (NRPS) LtxA protein condenses L-methyl-valine and L-tryptophan to form the linear dipeptide N-methyl-L-valyl-L-tryptophan. The latter is released via a NADPH-dependent reductive cleavage to form the aldehyde which is subsequently reduced to the corresponding alcohol. Then LtxB which is a P450-dependent monooxygenase serves as a catalyst in the oxidation and subsequent cyclization of N-methyl-L-valyl-L-tryptophan. Finally, LtxC which is a reverse prenyltransferase performs the transfer of a geranyl pyrophosphate (GPP) to carbon-7 of the indole ring which is accompanied by the loss of pyrophosphate.

Notes and References

  1. Cardellina . JH . Marner . FJ . Moore . RE . Apr 1979 . Seaweed dermatitis: structure of lyngbyatoxin A. . Science . 204 . 4389. 193–5 . 107586 . 10.1126/science.107586 . 1979Sci...204..193C .
  2. Fujiki . H . Mori . M . Nakayasu . M . Terada . M . Sugimura . T . Moore . RE . Jun 1981 . Indole alkaloids: dihydroteleocidin B, teleocidin, and lyngbyatoxin A as members of a new class of tumor promoters . Proceedings of the National Academy of Sciences USA . 78 . 6. 3872–6 . 6791164 . 319675 . 10.1073/pnas.78.6.3872. free . 1981PNAS...78.3872F .
  3. Kozikowski . AP . Shum . PW . Basu . A . Lazo . JS . Aug 1991 . Synthesis of structural analogues of lyngbyatoxin A and their evaluation as activators of protein kinase C. . Journal of Medicinal Chemistry . 34 . 8. 2420–30 . 1875340 . 10.1021/jm00112a017.
  4. Osborne . NJ . Webb . PM . Shaw . GR . Nov 2001 . The toxins of Lyngbya majuscula and their human and ecological health effects . Environment International . 27 . 5. 381–92 . 11757852 . 10.1016/s0160-4120(01)00098-8. 2001EnInt..27..381O .
  5. Ito . E . Satake . M . Yasumoto . T . May 2002 . Pathological effects of lyngbyatoxin A upon mice . Toxicon . 40 . 5. 551–6 . 11821127 . 10.1016/s0041-0101(01)00251-3.
  6. Edwards . DJ . William H. Gerwick . Gerwick . WH . 2004 . Lyngbyatoxin biosynthesis: sequence of biosynthetic gene cluster and identification of a novel aromatic prenyltransferase . Journal of the American Chemical Society . 126 . 37. 11432–3 . 15366877 . 10.1021/ja047876g .
  7. 10.1021/cb400189j . 8 . High-Titer Heterologous Production in E. coli of Lyngbyatoxin, a Protein Kinase C Activator from an Uncultured Marine Cyanobacterium . ACS Chemical Biology . 1888–1893. 3880125 . 23751865 . 2013 . Ongley . SE . Bian . X . Zhang . Y . Chau . R . Gerwick . WH . Müller . R . Neilan . BA. 9 .

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