Two new skeletal analogues of saxitoxin found in the scallop, Patinopecten yessoensis, as possible metabolites of paralytic shellfish toxins. (September 2021)

• Record Type: Journal Article
• Authors: Numano, Satoshi; Kudo, Yuta; Cho, Yuko; Konoki, Keiichi; Kaga, Yoshimasa; Nagasawa, Kazuo; Yotsu-Yamashita, Mari
• Is Part Of: Chemosphere. Volume 278(2021)
• Publication Date: 2021-09
• Subjects: Saxitoxin -- Paralytic shellfish toxins -- Scallop -- NMR -- Metabolites; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2021.130224
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: The scallop, Patinopecten yessoensis, was screened for new saxitoxin analogues to study the metabolism of paralytic shellfish toxins (PSTs), and this resulted in the discovery of two new analogues: M5-hemiaminal (HA) and M6-HA . M5-HA was isolated and its structure was determined by using NMR spectroscopy. It contains hydrogen at C-4 with opposite stereochemistry to that in saxitoxin, and a hemiaminal was formed between 9-NH2 and the hydrated ketone at C-12 in α-orientation. This is the first reported structural feature in a natural saxitoxin analogue, whereas the same ring system has previously been reported in a synthetic saxitoxin analogue, FD-saxitoxin. Acid hydrolysis of the carbamoyl N -sulfate in M5-HA produced M6-HA which was also identified in P. yessoensis by using LC-MSMS. M5-HA was not synthetically produced from M1 (11-hydroxy gonyautoxin-5) and M3 (11, 11-dihydroxy gonyautoxin-5) through incubation in aqueous buffers. Furthermore, PSTs in the hepatopancreas of P. yessoensis, cultured in a bay located in northeastern Japan, were chronologically analyzed in 2018. The highest concentrations of M1/M3/M5-HA were observed two weeks after C-toxins had reached their highest concentrations, which provides evidence that M1/M3/M5-HA are metabolites of C-toxins. The voltage-gated sodium channel blockage activity of M6-HA was not detected at the concentration of 140 nM by using the Neuro-2A veratridine/ouabain assay. Graphical abstract: Image 1 Highlights: Two new saxitoxin analogues, M5-HA and M6-HA were found in scallop. Structures of M5-HA and M6-HA were elucidated by using NMR and chemical derivatization. M5-HA and M6-HA were predicted to be derived from C2 in scallop. Chronological analysis of PSTs supported that M1/M3/M5-HA are metabolites of C2.