Six domoic acid related compounds from the red alga, Chondria armata, and domoic acid biosynthesis by the diatom, Pseudo-nitzschia multiseries

Abstract

Domoic acid (DA, 1), a potent neurotoxin that causes amnesic shellfish poisoning, has been found in diatoms and red algae. While biosynthetic pathway towards DA from geranyl diphosphate and l-glutamate has been previously proposed, its late stage is still unclear. Here, six novel DA related compounds, 7′-methyl-isodomoic acid A (2) and B (3), N-geranyl-l-glutamic acid (4), 7′-hydroxymethyl-isodomoic acid A (5) and B (6), and N-geranyl-3(R)-hydroxy-l-glutamic acid (7), were isolated from the red alga, Chondria armata, and their structures were determined. The compounds 4 and 7, linear compounds, are predictable as the precursors to form the DA pyrrolidine ring. The compounds 2 and 3 are thought as the cyclized products of 7; therefore, dehydration and electron transfer from the internal olefin of 7 is a possible mechanism for the pyrrolidine ring formation. One terminal methyl group of the side chain of 2 and 3 is predicted to be oxidized to hydroxymethyl (5, 6), and then to carboxylic acids, forming isodomoic acids A and B. Finally, the terminal olefin of isodomoic acid A would be isomerized to form DA. In addition, [15N, D]-labeled 4 was incorporated into DA using the diatom, Pseudo-nitzschia multiseries, demonstrating that 4 is the genuine precursor of DA.

Transcriptomic responses to grazing reveal the metabolic pathway leading to the biosynthesis of domoic acid and highlight different defense strategies in diatoms

“…The early findings have been confirmed and it was demonstrated that the amino function in DA is generated by nucleophilic displacement of GPP by an unknown intermediate [23]. Recently, six compounds with potential functions in the condensation of GPP and l-glutamate were identified and their structure described [24]. The same study also confirmed N-geranyl-l-glutamic acid as a potential intermediate.…”

Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection

“…Domoic acid (DA, Figure 1 B) is a naturally occurring excitotoxin originally isolated from the marine red alga Chondria armata and produced by the diatoms Nitzschia , Pseudo-nitzschia and Amphora [ 33 , 34 ]. These toxic diatoms are found in polar, temperate, subtropical and tropical regions and are responsible for many toxic blooms worldwide affecting coastal environments in Europe, America or Oceania [ 35 ].…”

Biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom

“…S6). Recently, L -NGG was isolated in low abundance from the DA-containing red alga Chondria armata and shown through labeling experiments in P. multiseries to be a precursor to DA (24). These observations further implicate dabA as a gene that encodes a major step in DA biosynthesis.…”

“…3A and figs. S7 and S8), of which 5a and 5b had been recently isolated from C. armata (24). DabC, however, showed minimal cyclization of other similarly N -prenylated glutamic acids (fig.…”