Lyngbyatoxin-a

Biosynthesis

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

References

1. (Apr 1979). "Seaweed dermatitis: structure of lyngbyatoxin A.". Science.
2. (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.
3. (Aug 1991). "Synthesis of structural analogues of lyngbyatoxin A and their evaluation as activators of protein kinase C.". Journal of Medicinal Chemistry.
4. (Nov 2001). "The toxins of Lyngbya majuscula and their human and ecological health effects". Environment International.
5. (May 2002). "Pathological effects of lyngbyatoxin A upon mice". Toxicon.
6. (2004). "Lyngbyatoxin biosynthesis: sequence of biosynthetic gene cluster and identification of a novel aromatic prenyltransferase". Journal of the American Chemical Society.
7. (2013). "High-Titer Heterologous Production in E. coli of Lyngbyatoxin, a Protein Kinase C Activator from an Uncultured Marine Cyanobacterium". ACS Chemical Biology.