학술논문

Biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom
Document Type
article
Source
Science. 361(6409)
Subject
Rare Diseases
Biotechnology
Genetics
Diatoms
Eutrophication
Kainic Acid
Multigene Family
Neurotoxins
Recombinant Proteins
General Science & Technology
Language
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.