Abstract
Saxitoxin and its analogues, paralytic shellfish toxins (PSTs), are potent and specific voltage-gated sodium channel blockers. These toxins are produced by some species of freshwater cyanobacteria and marine dinoflagellates. We previously identified several biosynthetic intermediates of PSTs, as well as new analogues, from such organisms and proposed the biosynthetic and metabolic pathways of PSTs. In this study, 12β-deoxygonyautoxin 5 (12α-gonyautoxinol 5 = gonyautoxin 5-12(R)-ol) was identified in the freshwater cyanobacterium, Dolichospermum circinale (TA04), and 12β-deoxysaxitoxin (12α-saxitoxinol = saxitoxin-12(R)-ol) was identified in the same cyanobacterium and in the marine dinoflagellate Alexandrium pacificum (Group IV) (120518KureAC) for the first time from natural sources. The authentic standards of these compounds and 12α-deoxygonyautoxin 5 (12β-gonyautoxinol 5 = gonyautoxin 5-12(S)-ol) were prepared by chemical derivatization from the major PSTs, C1/C2, produced in D. circinale (TA04). These standards were used to identify the deoxy analogues by comparing the retention times and MS/MS spectra using high-resolution LC-MS/MS. Biosynthetic or metabolic pathways for these analogues have also been proposed based on their structures. The identification of these compounds supports the α-oriented stereoselective oxidation at C12 in the biosynthetic pathway towards PSTs.
Highlights
Saxitoxin (STX, 1, Figure 1) is one of the most potent voltage-gated sodium channel (Nav ) blockers [1]
The first biosynthetic study of STX was a feeding experiment conducted by Shimizu et al [9], in which stable isotope-labeled acetic acid and amino acids were used as essential substrates for paralytic shellfish toxins (PSTs)-producing cyanobacteria and dinoflagellates
A. pacificum (Group IV) (120518KureAC) at 12.8 min on the Extracted ion chromatograms (EIC) of reversed phase (RP)-LCMS detected at m/z 284.1466 ± 0.02 ([M + H]+ ; C10 H18 N7 O3 ); HRMS ([M + H]+ m/z 284.1443 for TA04, and m/z 284.1463 for 120518KureAC), which was supposed to be the deoxy analogue of STX
Summary
Saxitoxin (STX, 1, Figure 1) is one of the most potent voltage-gated sodium channel (Nav ) blockers [1]. Our group identified biosynthetic intermediates of STX, such as Int-A0 , Int-C0 2, 11-hydroxy Int-C0 2, Int-E0 , and a shunt compound, Cyclic-C0 , in the PST-producing cyanobacterium Dolichospermum circinale (formerly described as Anabaena circinalis) (TA04), and the PST-producing dinoflagellate Alexandrium catenella (Group I) (formerly described as Alexandrium tamarense) (Axat-2), using LCMS with synthetic standards and by feeding experiments [12–15]. Six STX analogues, namely LWTX1-6, were isolated from the freshwater cyanobacterium Microseira wollei (formerly described as Lyngbya wollei), and their corresponding chemical structures were determined by NMR spectroscopic analysis by Onodera et al (Figure 1) [26] Three of these analogues have an α-hydroxyl group instead of a hydrated ketone at C12 in STX, and five of them contain an O-acetyl moiety at.
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