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

John K Brunson; Shaun M K McKinnie; Jonathan R Chekan; John P McCrow; Zachary D Miles; Erin M Bertrand; Vincent A Bielinski; Hanna Luhavaya; Miroslav Oborník; G Jason Smith; David A Hutchins; Andrew E Allen; Bradley S Moore

doi:10.1126/science.aau0382

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

Science. 2018 Sep 28;361(6409):1356-1358. doi: 10.1126/science.aau0382.

Authors

John K Brunson^{1

2}, Shaun M K McKinnie¹, Jonathan R Chekan¹, John P McCrow², Zachary D Miles¹, Erin M Bertrand^{2

3}, Vincent A Bielinski⁴, Hanna Luhavaya¹, Miroslav Oborník⁵, G Jason Smith⁶, David A Hutchins⁷, Andrew E Allen^{8

9}, Bradley S Moore^{10

11}

Affiliations

¹ Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093, USA.
² Microbial and Environmental Genomics Group, J. Craig Venter Institute, La Jolla, CA 92037, USA.
³ Department of Biology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
⁴ Synthetic Biology and Bioenergy Group, J. Craig Venter Institute, La Jolla, CA 92037, USA.
⁵ Institute of Parasitology, University of South Bohemia and Biology Center CAS, Branišovská 31, 370 05 České Budějovice, Czech Republic.
⁶ Moss Landing Marine Laboratories, 8272 Moss Landing Road, Moss Landing, CA 95039, USA.
⁷ Marine and Environmental Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
⁸ Microbial and Environmental Genomics Group, J. Craig Venter Institute, La Jolla, CA 92037, USA. [email protected] [email protected].
⁹ Integrative Oceanography Division, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92037, USA.
¹⁰ Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093, USA. [email protected] [email protected].
¹¹ Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.

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 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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Diatoms / genetics
Diatoms / metabolism*
Eutrophication*
Kainic Acid / analogs & derivatives*
Kainic Acid / chemistry
Kainic Acid / metabolism
Multigene Family
Neurotoxins / biosynthesis*
Neurotoxins / genetics
Recombinant Proteins / genetics
Recombinant Proteins / metabolism

Substances

Neurotoxins
Recombinant Proteins
domoic acid
Kainic Acid

Abstract

Publication types

MeSH terms

Substances

Grants and funding