TY - JOUR
T1 - Domoic acid biosynthesis in the red alga Chondria armata suggests a complex evolutionary history for toxin production
AU - Steele, Taylor S.
AU - Brunson, John K.
AU - Maeno, Yukari
AU - Terada, Ryuta
AU - Allen, Andrew E.
AU - Yotsu-Yamashita, Mari
AU - Chekan, Jonathan R.
AU - Moore, Bradley S.
N1 - Funding Information:
ACKNOWLEDGMENTS. We thank T. Michael (Salk Institute for Biological Studies) for assistance with DNA sequencing, G. J. Smith (Moss Landing Marine Laboratories) for providing the diatom image, T. Teruya (University of Ryukyus) and G. Saunders (University of New Brunswick) for providing seaweed images, and G. Rouse and T. Fallon (Scripps Institution of Oceanography) for helpful discussions. We acknowledge R. Botts (Point Loma Nazarene University) for his valuable mentorship and guidance. This research was supported by the National Oceanic and Atmospheric Administration (NA19NOS4780181 to B.S.M. and A.E.A.), the NSF through the Graduate Fellowship Research Program to T.S.S., the NIH (F31ES030613 to J.K.B.), the Simons Foundation Fellowship of the Life Sciences Research Foundation to J.R.C., and the University of North Carolina at Greensboro research startup funds to J.R.C.
Funding Information:
We thank T. Michael (Salk Institute for Biological Studies) for assistance with DNA sequencing, G. J. Smith (Moss Landing Marine Laboratories) for providing the diatom image, T. Teruya (University of Ryukyus) and G. Saunders (University of New Brunswick) for providing seaweed images, and G. Rouse and T. Fallon (Scripps Institution of Oceanography) for helpful discussions. We acknowledge R. Botts (Point Loma Nazarene University) for his valuable mentorship and guidance. This research was supported by the National Oceanic and Atmospheric Administration (NA19NOS4780181 to B.S.M. and A.E.A.), the NSF through the Graduate Fellowship Research Program to T.S.S., the NIH (F31ES030613 to J.K.B.), the Simons Foundation Fellowship of the Life Sciences Research Foundation to J.R.C., and the University of North Carolina at Greensboro research startup funds to J.R.C.
Publisher Copyright:
© This article is distributed under Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND).
PY - 2022/2/8
Y1 - 2022/2/8
N2 - 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.
AB - 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.
KW - Biosynthetic gene cluster
KW - Genomics
KW - Natural products
KW - Neurotoxin
KW - Seaweed
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U2 - 10.1073/pnas.2117407119
DO - 10.1073/pnas.2117407119
M3 - Article
C2 - 35110408
AN - SCOPUS:85124061902
SN - 0027-8424
VL - 119
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 6
M1 - e2117407119
ER -