Chemistry, biology, and toxicology of domoic acid and its isomers.

The causative agent of toxicity in cultured mussels from a localized area of eastern Prince Edward Island has been identified as domoic acid, a neuroexcitatory amino acid. The toxin was isolated by a number of different bioassay-directed separation techniques including high-performance liquid chromatography (HPLC), high-voltage paper electrophoresis (HVPE), and ion-exchange chromatography, and characterized by a number of spectroscopic techniques including ultraviolet, infrared, mass spectrometry, and nuclear magnetic resonance. The isolation and purification methods are described in detail and some new analytical data for domoic acid are reported. A plankton bloom at the time of the outbreak gave positive mouse bioassays and consisted almost entirely of the pennate diatom, Nitzschia pungens f. multiseries. A positive correlation was found between the number of N. pungens cells and the concentration of domoic acid in the plankton. N. pungens f. multiseries isolated from Cardigan Bay produced domoic acid de novo during stationary phase culture at levels (1 to 10 pg/cell) comparable to values estimated for N. pungens in the plankton samples. We conclude that N. pungens was the major source of the domoic acid in toxic mussels in eastern Prince Edward Island. The recurrence, in November 1988, of a monospecific bloom of N. pungens and the presence of domoic acid in plankton and mussels reinforces this conclusion.