Frontier Research Institute for Interdisciplinary Sciences
Tohoku University


Discovery of two new natural compounds related to tetrodotoxin from toxic newt


Tetrodotoxin (TTX), one of the most famous toxin, is distributed worldwide in marine and terrestrial animals such as pufferfish, snails, newts and frogs. Its complex chemical structure and potent toxicity has been fascinating scientists in various research fields for a long time. Despite the intense interest in TTX, a question “How this unique toxin is biosynthesized in nature?” has not been resolved. Since the true producer of TTX is ambiguous, the genetic information regarding biosynthesis of TTX is not available at all.

Dr. Yuta Kudo, Assistant Professor of Frontier Research Institute for Interdisciplinary Sciences, and Dr. Mari Yotsu-Yamashita, Professor of Graduate School of Agricultural Science, discovered two new natural compounds related to tetrodotoxin from toxic newt. The biosynthetic pathway of TTX in terrestrial environments was proposed/discussed based the structures of new compounds and the series of putative biosynthetic intermediates of TTX collected by them in previous studies. In addition, the voltage-gated sodium ion channel blocking activity of new compound was evaluated by cell-based assay, and the value was compared with TTX and its known analog. These results may shed light on a mystery of biosynthesis of TTX and proceed the structure-activity relationship study of TTX. The article reporting these results published in “Journal of Natural Products” as ASAP on May 22, 2019.
 Publication Details
Yuta Kudo and Mari Yotsu-Yamashita* (*corresponding author)
 "Isolation and Biological Activity of 8-Epitetrodotoxin and the Structure of a Possible Biosynthetic Shunt Product of Tetrodotoxin, Cep-226A, from the Newt Cynops ensicauda popei"
Journal of Natural Products
doi: 10.1021/acs.jnatprod.9b00178