Lyngbyatoxin-a

Lyngbyatoxin-a

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
CAS Number	70497-14-2
3D model (Jmol)	Interactive image
ChemSpider	10472344
PubChem	91706
InChI 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 Key: KISDGNGREAJPQR-OICBGKIFSA-N 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
SMILES 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
Chemical formula	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).
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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 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

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. line feed character in |title= at position 65 (help)