2018
DOI: 10.1126/science.aau0382
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Biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom

Abstract: Oceanic 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 mechanis… Show more

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Cited by 137 publications
(170 citation statements)
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“…[18,21,22] The kab gene clustering is consistent with early examples of red algae clustering genes. Many organisms,i ncluding bacteria, fungi, plants,and unicellular algae,are known to cluster genes from the same biosynthetic pathway.…”
supporting
confidence: 77%
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“…[18,21,22] The kab gene clustering is consistent with early examples of red algae clustering genes. Many organisms,i ncluding bacteria, fungi, plants,and unicellular algae,are known to cluster genes from the same biosynthetic pathway.…”
supporting
confidence: 77%
“…By scaling up the GfKabC reaction, we could isolate this product in sufficient yield to characterize it by NMR spectroscopy,which identified this product as kainic acid lactone ( Figure 2B). While the biochemical basis for this differential product distribution is an ongoing focus of study,w e suggest achemical mechanism analogous to that proposed for DabC [18] that diverges following pyrrolidine ring formation to rationalize the observed chemotype (Supporting Information, Figure S9). In contrast to the agonistic activity of kainic acid, kainic acid lactone has been shown to be an iGluR antagonist.…”
mentioning
confidence: 85%
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