lnterspecies distribution and biogenetic origin of tetrodotoxin and its derivatives

Screening for tetrodotoxin among biota at low levels of the food chain led us to identification of bacteria as the primary source of the toxin. In parallel with the search for the biogenetic origin, we explored naturally occurring tetrodotoxin analogues which might shed light on the biogenetic pathways of the toxin. Isolation of 6-epitetrodotoxin and 11-deoxytetrodotoxin from the newt Cynops ensicauda suggested that tetrodotoxin biosynthesis involves an isoprenoid C5 unit. Puffers contained ll-nortetrodotoxin-6(R)-ol, in addition to tetrodotoxin and the two analogues found in newts. Addition of trifluoroacetic acid-d to the NMR solvent resolved NMR signals and thus allowed us to assign for the first time all proton and carbon NMR signals of tetrodotoxin and its analogues.