First identification of 5,11-dideoxytetrodotoxin in marine animals, and characterization of major fragment ions of tetrodotoxin and its analogs by high resolution ESI-MS/MS

Mari Yotsu-Yamashita, Yuka Abe, Yuta Kudo, Raphael Ritson-Williams, Valerie J. Paul, Keiichi Konoki, Yuko Cho, Masaatsu Adachi, Takuya Imazu, Toshio Nishikawa, Minoru Isobe

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

Even though tetrodotoxin (TTX) is a widespread toxin in marine and terrestrial organisms, very little is known about the biosynthetic pathway used to produce it. By describing chemical structures of natural analogs of TTX, we can start to identify some of the precursors that might be important for TTX biosynthesis. In the present study, an analog of TTX, 5,11-dideoxyTTX, was identified for the first time in natural sources, the ovary of the pufferfish and the pharynx of a flatworm (planocerid sp. 1), by comparison with totally synthesized (-)-5,11-dideoxyTTX, using high resolution ESI-LC-MS. Based on the presence of 5,11-dideoxyTTX together with a series of known deoxy analogs, 5,6, 11-trideoxyTTX, 6,11-dideoxyTTX, 11-deoxyTTX, and 5-deoxyTTX, in these animals, we predicted two routes of stepwise oxidation pathways in the late stages of biosynthesis of TTX. Furthermore, high resolution masses of the major fragment ions of TTX, 6,11-dideoxyTTX, and 5,6,11-trideoxyTTX were also measured, and their molecular formulas and structures were predicted to compare them with each other. Although both TTX and 5,6,11-trideoxyTTX give major fragment ions that are very close, m/z 162.0660 and 162.1020, respectively, they are distinguishable and predicted to be different molecular formulas. These data will be useful for identification of TTXs using high resolution LC-MS/MS.

Original languageEnglish
Pages (from-to)2799-2813
Number of pages15
JournalMarine Drugs
Volume11
Issue number8
DOIs
Publication statusPublished - 2013 Aug

Keywords

  • 5,11-dideoxytetrodotoxin
  • Biosynthesis
  • LC-MS/MS
  • Tetrodotoxin

ASJC Scopus subject areas

  • Drug Discovery

Fingerprint

Dive into the research topics of 'First identification of 5,11-dideoxytetrodotoxin in marine animals, and characterization of major fragment ions of tetrodotoxin and its analogs by high resolution ESI-MS/MS'. Together they form a unique fingerprint.

Cite this