Biosynthetic pathway identified for algal bloom toxin domoic acid

When the microalgae known as diatoms form blooms, they sometimes produce the powerful neurotoxin domoic acid. But not all diatoms produce the toxin, and even species that can don’t always do so. Predicting which blooms will produce the toxins is tough because the pathway through which the toxin is made has remained unknown.

Now, Bradley S. Moore of the University of California, San Diego; Andrew E. Allen of the J. Craig Venter Institute; and coworkers have identified most of the domoic acid-making enzymes in the diatom Pseudo-nitzschia multiseries (Science 2018, DOI: 10.1126/science.aau0382). They hope to use the information to predict which blooms will produce domoic acid so they can anticipate exposure risks for humans and marine organisms.

The researchers identified genes with elevated activity under conditions known to stimulate domoic acid production—limited phosphate and elevated carbon dioxide. They identified a cluster of four genes as the most likely candidates.

One of those genes encodes an enzyme that catalyzes the N-prenylation of l-glutamic acid with geranyl pyrophosphate to form N-geranyl-l-glutamic acid. Two others encode enzymes that oxidize and cyclize the glutamic acid derivative to form isodomoic acid. The researchers have not yet identified an enzyme that catalyzes the final isomerization to the neurotoxin.

The work is “a major breakthrough in discerning how a subset of marine diatoms is able to produce domoic acid, a neurotoxin that can be biomagnified through marine food webs,” says E. Virginia Armbrust, a phytoplankton expert at the University of Washington. “This work is a game changer for understanding ecosystem health,” she says.

Kathi Lefebvre, an expert on algal toxins at the Northwest Fisheries Science Center, says the work “will allow for new research studies to identify the triggers for activation and regulation of those genes that can then be used to predict toxin production in blooms.”

Moore and his colleagues hope to be able to do just that by measuring expression levels of the genes in the ocean. “Such information would be of critical importance to the public and the economy of nearshore fisheries,” Moore says.