Lyngbyatoxin-a

Last updated
Lyngbyatoxin-a
Lyngbyatoxin A.svg
Names
Preferred IUPAC name
(2S,5S)-9-[(3R)-3,7-Dimethylocta-1,6-dien-3-yl]-5-(hydroxymethyl)-1-methyl-2-(propan-2-yl)-1,2,4,5,6,8-hexahydro-3H-[1,4]diazonino[7,6,5-cd]indol-3-one
Other names
Lyngbyatoxin-a
Identifiers
  • 70497-14-2 Yes check.svgY
3D model (JSmol)
ChemSpider
PubChem CID
UNII
  • InChI=1S/C27H39N3O2/c1-8-27(6,13-9-10-17(2)3)21-11-12-22-23-19(15-28-24(21)23)14-20(16-31)29-26(32)25(18(4)5)30(22)7/h8,10-12,15,18,20,25,28,31H,1,9,13-14,16H2,2-7H3,(H,29,32)/t20-,25-,27-/m0/s1 X mark.svgN
    Key: KISDGNGREAJPQR-OICBGKIFSA-N X mark.svgN
  • InChI=1/C27H39N3O2/c1-8-27(6,13-9-10-17(2)3)21-11-12-22-23-19(15-28-24(21)23)14-20(16-31)29-26(32)25(18(4)5)30(22)7/h8,10-12,15,18,20,25,28,31H,1,9,13-14,16H2,2-7H3,(H,29,32)/t20-,25-,27-/m0/s1
    Key: KISDGNGREAJPQR-OICBGKIFBW
  • CN([C@H]1C(C)C)C2=C3C(NC=C3C[C@@H](CO)NC1=O)=C([C@](C=C)(C)CC/C=C(C)/C)C=C2
Properties
C27H39N3O2
Molar mass 437.628 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)
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

Lyngbyatoxin Biosynthesis reported by Gerwick et al. and Neilan et al. Lyngbyatoxin Biosynthesis2.png
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.

Related Research Articles

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Cyclopiazonic acid Chemical compound

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<i>Moorea producens</i> Species of bacterium

Moorea producens is a species of filamentous cyanobacteria in the genus Moorea, including tropical marine strains formerly classified as Lyngbya majuscula due to morphological resemblance but separated based on genetic evidence. Moorea producens grows on seagrass and is one of the causes of the human skin irritation seaweed dermatitis. It is known as fireweed in Australia and stinging limu in Hawaii.

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Scytonemin Chemical compound

Scytonemin is a secondary metabolite and an extracellular matrix (sheath) pigment synthesized by many strains of cyanobacteria, including Nostoc, Scytonema, Calothrix, Lyngbya, Rivularia, Chlorogloeopsis, and Hyella. Scytonemin-synthesizing cyanobacteria often inhabit highly insolated terrestrial, freshwater and coastal environments such as deserts, semideserts, rocks, cliffs, marine intertidal flats, and hot springs.

Apratoxin A Chemical compound

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<i>Lyngbya majuscula</i> Species of bacterium

Lyngbya majuscula is a species of filamentous cyanobacteria in the genus Lyngbya. It is named after the Dane Hans Christian Lyngbye.

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Antillatoxin Chemical compound

Antillatoxin (ATX) is a potent lipopeptide neurotoxin produced by the marine cyanobacterium Lyngbya majuscula. ATX activates voltage-gated sodium channels, which can cause cell depolarisation, NMDA-receptor overactivity, excess calcium influx and neuronal necrosis.

Debromoaplysiatoxin Chemical compound

Debromoaplysiatoxin is a toxic agent produced by the blue-green alga Lyngbya majuscula. This alga lives in marine waters and causes seaweed dermatitis. Furthermore, it is a tumor promoter which has an anti-proliferative activity against various cancer cell lines in mice.

Pyonitrin Chemical compound

The Pyonitrins are a family of highly hydrogen-deficient alkaloids discovered from an insect-associated Pseudomonas protegens strain. In vivo, pyonitrins A-D show activity against pathogen Candida albicans, which commonly cause bloodstream infections.

References

  1. Cardellina, JH; Marner, FJ; Moore, RE (Apr 1979). "Seaweed dermatitis: structure of lyngbyatoxin A.". Science. 204 (4389): 193–5. doi:10.1126/science.107586. PMID   107586.
  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. doi: 10.1073/pnas.78.6.3872 . PMC   319675 . PMID   6791164.
  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. doi:10.1021/jm00112a017. PMID   1875340.
  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. doi:10.1016/s0160-4120(01)00098-8. PMID   11757852.
  5. Ito, E; Satake, M; Yasumoto, T (May 2002). "Pathological effects of lyngbyatoxin A upon mice". Toxicon. 40 (5): 551–6. doi:10.1016/s0041-0101(01)00251-3. PMID   11821127.
  6. Edwards, DJ; 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. doi:10.1021/ja047876g. PMID   15366877.
  7. Ongley, SE; Bian, X; Zhang, Y; Chau, R; Gerwick, WH; Müller, R; Neilan, BA (2013). "High-Titer Heterologous Production in E. coli of Lyngbyatoxin, a Protein Kinase C Activator from an Uncultured Marine Cyanobacterium". ACS Chemical Biology. 8 (9): 1888–1893. doi:10.1021/cb400189j. PMC   3880125 . PMID   23751865.