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

Brunson, JK, McKinnie SMK, Chekan JR, McCrow JP, Miles ZD, Bertrand EM, Bielinski VA, Luhavaya H, Oborník M, Smith JG, Hutchins DA, Allen AE, Moore BS.  2018.  Biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom. Science. 361:1356-1358.

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Algal blooms can devastate marine mammal communities through the production of neurotoxins that accumulate within the food web. Brunson et al. identified a cluster of genes associated with biosynthesis of the neurotoxin domoic acid in a marine diatom (see the Perspective by Pohnert et al.). In vitro experiments established a series of enzymes that create the core structure of the toxin. Knowledge of the genes involved in domoic acid production will allow for genetic monitoring of algal blooms and aid in identifying conditions that trigger toxin production.Science, this issue p. 1356; see also p. 1308Oceanic harmful algal blooms of Pseudo-nitzschia diatoms produce the potent mammalian neurotoxin domoic acid (DA). Despite decades of research, the molecular basis for its biosynthesis is not known. By using growth conditions known to induce DA production in Pseudo-nitzschia multiseries, we implemented transcriptome sequencing in order to identify DA biosynthesis genes that colocalize in a genomic four-gene cluster. We biochemically investigated the recombinant DA biosynthetic enzymes and linked their mechanisms to the construction of DA’s diagnostic pyrrolidine skeleton, establishing a model for DA biosynthesis. Knowledge of the genetic basis for toxin production provides an orthogonal approach to bloom monitoring and enables study of environmental factors that drive oceanic DA production.