Lyngbyatoxin-a

Lyngbyatoxin-a
Names
Systematic 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
3D model (JSmol)
ChemSpider
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 markN
    Key: KISDGNGREAJPQR-OICBGKIFSA-N X markN
  • 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).
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Lyngbyatoxin-a is a type of alkaloid cyanotoxin produced by certain cyanobacteria species, most notably Moorea producens (formerly classified as 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.

Biosynthesis

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

Lyngbyatoxin is a terpenoid indole alkaloid hybrid that belongs to the class of non-ribosomal peptides (NRPs). 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. A P450-dependent monooxygenase called LtxB then performs the oxidation and subsequent cyclization of N-methyl-L-valyl-L-tryptophan. Finally, LtxC transfers a geranyl functional group from geranyl pyrophosphate (GPP) to carbon number 7 of the indole ring.

References

  1. ↑ Cardellina, JH; Marner, FJ; Moore, RE (Apr 1979). "Seaweed dermatitis: structure of lyngbyatoxin A.". Science. 204 (4389): 193–5. Bibcode:1979Sci...204..193C. 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. Bibcode:1981PNAS...78.3872F. 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. Bibcode:2001EnInt..27..381O. 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.