Proposed Biotransformation Pathways for New Metabolites of Paralytic Shellfish Toxins Based on Field and Experimental Mussel Samples

Abstract

A seafood poisoning event occurred in Qinhuangdao, China, in April 2016. Subsequently, the causative mussels (Mytilus galloprovincialis) were harvested and analyzed to reveal a high concentration [∼10 758 μg of saxitoxin (STX) equiv kg] of paralytic shellfish toxins (PSTs), including gonyautoxin (GTX)1/4 and GTX2/3, as well as new metabolites 11-hydroxy-STX (M2), 11,11-dihydroxy-STX (M4), open-ring 11,11-dihydroxy-STX (M6), 11-hydroxy-neosaxitoxin (NEO) (M8), and 11,11-dihydroxy-NEO (M10). To understand the origin and biotransformation pathways of these new metabolites, uncontaminated mussels (M. galloprovincialis) were fed with either of two Alexandrium tamarense strains (ATHK and TIO108) under laboratory conditions. Similar PST metabolites were also detected in mussels from both feeding experiments. Results supposed that 11-hydroxy-C2 toxin (M1) and 11,11-dihydroxy-C2 (M3) are transformed from C2, while 11-hydroxy-C4 toxin (M7) and 11,11-dihydroxy-C4 (M9) are converted from C4. In addition, the metabolites M2, M4, and M6 appear to be products of GTX2/3, and the metabolites M8 and M10 are likely derived from GTX1/4.

Marine natural products

“…641 Feeding two strains of the dinoagellate Alexandrium tamarense to uncontaminated mussels Mytilus galloprovincialis led to detection of known and new paralytic shellsh toxins related to saxitoxin. 642 The roles and substrate selectivity of Octopus vulgaris proteins Scd and Evol4 as fatty acid desaturase and elongase enzymes, respectively, have been studied. 643 The cone snail Conus pulicarius was the source of the moderately cytotoxic steroidal glycosides 1425-1427.…”

Paralytic shellfish toxin profiles in mussel, cockle and razor shell under post-bloom natural conditions: Evidence of higher biotransformation in razor shells and cockles

“…and dcSTX, respectively, may occur in the presence of a carbamoylase enzyme, through the hydrolysis of the benzoate group . In addition, the conversion of C1+2 and C3+4 into M1 and M7 toxins, respectively, by desulfation of the 11-hydroxysulfate group and the conversion of GTX5 into M1, by hydroxylation of the same group, should also be considered (Qiu et al, 2018;Ding et al, 2017;Li et al, 2012;Vale, 2010).…”

“…The most studied analogues are divided into three families, according to their side chains: carbamoil (saxitoxin-STX, neosaxitoxin-NEO and gonyautoxins-GTX1 to GTX4), N-sulfocarbamoil (GTX5, GTX6 and C1 to C4) and decarbamoil (dcGTX1 to dcGTX4, dcSTX and dcNEO) (Oshima, 1995a). Other families have been identified, such as deoxydecarbamoil (doSTX, doGTX2 and doGTX3), hydroxy-and sulfate-benzoate toxins (GC toxins), and hydroxylated saxitoxins (M toxins), whose origin and biosynthesis pathway is not yet fully understood (Qiu et al, 2018;Ding et al, 2017;Li et al, 2012;Vale, 2010;Wiese et al, 2010;Dell'Aversano et al, 2008;Negri et al, 2007Negri et al, , 2003. Bivalves as filter feeding organisms may accumulate and biotransform those compounds in their tissues during toxic algal blooms (Bricelj and Shumway, 1998).…”

“…Due to the diverse biotransformation and metabolic pathways, toxin composition of contaminated bivalves in general differs from the corresponding PST producing phytoplankton (Ding et al, 2017;Marsden et al, 2016;Vale, 2010;Samsur et al, 2006;Silvert et al, 1998;Oshima et al, 1990). In bivalves, PST profiles are affected by the balance between the uptake of toxic phytoplankton cells, toxin transformation and elimination.…”

“…Biotransformation of toxins in bivalves may occur as a result of epimerization, oxidation, reduction, desulfation and hydrolysis reactions, enzymatic action, and also as a consequence of transformation by bacteria present in their digestive tract (Qiu et al, 2018;Ding et al, 2017;Turner et al, 2013;Donovan et al, 2009;Artigas et al, 2007;Fast et al, 2006;Smith et al, 2001;Murakami et al, 1999;Oshima, 1995b;Kotaki et al, 1985;Shimizu and Yoshioka, 1981). Biotransformation processes play an important role on the toxin excretion, leading to possible differences in toxicity and depuration kinetics among bivalve species (Bricelj and Shumway, 1998).…”