Structures of N -Hydroxy-Type Tetrodotoxin Analogues and Bicyclic Guanidinium Compounds Found in Toxic Newts
Year: 2020
Type: article
Abstract: The biosynthesis of tetrodotoxin (TTX, 1), a potent neurotoxin widely distributed in marine and terrestrial metazoans, remains unresolved. A significant issue has been identifying intermediates and shunt products associated with the biosynthetic pathway of TTX. We investigated TTX biosynthesis by screening and identifying new TTX-related compounds from Cynops ensicauda popei and Taricha granulosa. Mass spectrometry (MS)-guided screening identified two new N-hydroxy TTX analogues in newts: 1-hydroxy-8-epiTTX (2) and 1-hydroxy-8-epi-5,11-dideoxyTTX (3, previously reported as 1-hydroxy-5,11-dideoxyTTX). We prepared a new analogue, 8-epi-5,11-dideoxyTTX (4), from 3 via N-OH reduction and confirmed the presence of 4 in T. granulosa using hydrophilic interaction liquid chromatography (HILIC)-LCMS. The presence of 8-epi-type TTX analogues in both Cynops and Taricha supports a branched biosynthetic pathway of terrestrial TTX, which produces 6- and 8-epimers. In addition, new bicyclic guanidinium compounds Tgr-238 (5) and Tgr-240 (6) were identified as putative shunt products of our proposed TTX biosynthesis pathway. A structural analysis of Cep-228A (7), another bicyclic compound, was performed using NMR. Based on the structures of 5–7 and their analogues, we propose a model of the shunt and metabolic pathways of the terrestrial TTX biosynthesis.
Source: Journal of Natural Products
Language: English
Subfield: Environmental Chemistry
Field: Environmental Science
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,000
Awards: Elucidation of the biosynthetic pathway of terrestrial tetrodotoxin via metagenomic analysis, Identification of tetrodotoxin in marine sediments and screening for its biosynthetic genes in marine soil bacteria, G2712646973, G3997512798, G4281583466, Elucidation of biosynthesis of tetrodotoxin and saxitoxin based on chemical study, G5382158739, Investigation of the origin and biosynthesis of the terrestrial tetrodotoxin based on the chemical and metagenome analyses, G8385941278
OpenAlex ID: W3084023263