Lyngbyatoxin-a

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Lyngbyatoxin-a
Lyngbyatoxin A.svg
Names
IUPAC name
(4S,7S)-11-((R)-3,7-dimethylocta-1,6-dien-3-yl)-4-(hydroxymethyl)-7-isopropyl-8-methyl-4,5,7,8-tetrahydro-1H-[1,4]diazonino[7,6,5-cd]indol-6(3H)-one
Other names
Lyngbyatoxin-a
Identifiers
3D model (JSmol)
ChemSpider
Properties
C27H39N3O2
Molar mass 437.63 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
No verify (what is YesYNo ?)
Infobox references

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[edit]

Lyngbyatoxin Biosynthesis reported by Gerwick et al. and Neilan et al.

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 lost of pyrophosphate.

References[edit]

  1. ^ Cardellina JH 2nd, Marner FJ, Moore RE. Seaweed dermatitis: structure of lyngbyatoxin A. Science. 1979 Apr 13;204(4389):193-5. PMID 107586
  2. ^ Fujiki H, Mori M, Nakayasu M, Terada M, Sugimura T, Moore RE. 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. 1981 Jun;78(6):3872-6. PMID 6791164
  3. ^ Kozikowski AP, Shum PW, Basu A, Lazo JS. Synthesis of structural analogues of lyngbyatoxin A and their evaluation as activators of protein kinase C. Journal of Medicinal Chemistry. 1991 Aug;34(8):2420-30. PMID 1875340
  4. ^ Osborne NJ, Webb PM, Shaw GR. The toxins of Lyngbya majuscula and their human and ecological health effects. Environment International. 2001 Nov;27(5):381-92. PMID 11757852
  5. ^ Ito E, Satake M, Yasumoto T. Pathological effects of lyngbyatoxin A upon mice. Toxicon. 2002 May;40(5):551-6. PMID 11821127
  6. ^ Edwards DJ, Gerwick WH. Lyngbyatoxin biosynthesis: sequence of biosynthetic gene cluster and identification of a novel aromatic prenyltransferase. Journal of the American Chemical Society. 2004 Sep 22;126(37):11432-3. PMID 15366877
  7. ^ "High-Titer Heterologous Production in E. coli of Lyngbyatoxin, a Protein Kinase C Activator from an Uncultured Marine Cyanobacterium". ACS Chemical Biology. 8: 1888–1893. doi:10.1021/cb400189j. PMC 3880125Freely accessible.