Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 119, Issue 6, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2117407119
Keywords
natural products; neurotoxin; genomics; seaweed; biosynthetic gene cluster
Categories
Funding
- National Oceanic and Atmospheric Administration [NA19NOS4780181]
- NSF through the Graduate Fellowship Research Program
- NIH [F31ES030613]
- Simons Foundation Fellowship of the Life Sciences Research Foundation
- University of North Carolina at Greensboro research startup funds
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The biosynthetic pathways of domoic acid differ between diatoms and red macroalgae, with the absence of a critical enzyme in red macroalgae. Red macroalgae produce domoic acid via isodomoic acid B, with a unique origin of the rad genes compared to diatoms. The production of domoic acid in diatoms and red macroalgae involves a combination of native eukaryotic CYP450 neofunctionalization and horizontal gene transfer.
Domoic acid (DA), the causative agent of amnesic shellfish poisoning, is produced by select organisms within two distantly related algal clades: planktonic diatoms and red macroalgae. The biosynthetic pathway to isodomoic acid A was recently solved in the harmful algal bloom-forming diatom Pseudonitzschia multiseries, establishing the genetic basis for the global production of this potent neurotoxin. Herein, we sequenced the 507-Mb genome of Chondria armata, the red macroalgal seaweed from which DA was first isolated in the 1950s, identifying several copies of the red algal DA (rad) biosynthetic gene cluster. The rad genes are organized similarly to the diatom DA biosynthesis cluster in terms of gene synteny, including a cytochrome P450 (CYP450) enzyme critical to DA production that is notably absent in red algae that produce the simpler kainoid neurochemical, kainic acid. The biochemical characterization of the N-prenyltransferase (RadA) and kainoid synthase (RadC) enzymes support a slightly altered DA biosynthetic model in C. armata via the congener isodomoic acid B, with RadC behaving more like the homologous diatom enzyme despite higher amino acid similarity to red algal kainic acid synthesis enzymes. A phylogenetic analysis of the rad genes suggests unique origins for the red macroalgal and diatom genes in their respective hosts, with native eukaryotic CYP450 neofunctionalization combining with the horizontal gene transfer of N-prenyltransferases and kainoid synthases to establish DA production within the algal lineages.
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