Lyngbyatoxin Biosynthesis reported by Gerwick et al. and Neilan et al.
Lyngbyatoxin is a terpenoidindole alkaloid hybrid that belongs to the class of non-ribosomal peptides (NRPs).[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. A P450-dependent monooxygenase called LtxB then preforms the oxidation and subsequent cyclization of N-methyl-L-valyl-L-tryptophan. Finally, LtxC transfers a geranylfunctional group from geranyl pyrophosphate (GPP) to carbon number 7 of the indole ring.
^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. PMID1875340.
^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. PMID15366877.
