The lyngbyatoxins are potent skin irritants produced by Lyngbya majuscula and cause a condition known as "Swimmer's Itch" off Honolulu, HI. Reported is the molecular cloning of the lyngbyatoxin (ltx) biosynthetic gene cluster from L. majuscula using a strategy based on its predicted nonribosomal peptide synthetase (NRPS) assembly. The biosynthetic gene cluster spans 11.3 kilobase pairs and encodes for a two-module NRPS (LtxA), a P450 monooxygenase (LtxB), an aromatic prenyltransferase (LtxC), and an oxidase/reductase protein (LtxD). LtxC was heterologously produced and purified from E. coli and shown to catalyze the transfer of a geranyl group to (-)-indolactam V as the final step in the biosynthesis of lyngbyatoxin A.