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- Title
Scalable Biosynthesis of the Seaweed Neurochemical, Kainic Acid.
- Authors
Chekan, Jonathan R.; McKinnie, Shaun M. K.; Moore, Malia L.; Poplawski, Shane G.; Michael, Todd P.; Moore, Bradley S.
- Abstract
Kainic acid, the flagship member of the kainoid family of natural neurochemicals, is a widely used neuropharmacological agent that helped unravel the key role of ionotropic glutamate receptors, including the kainate receptor, in the central nervous system. Worldwide shortages of this seaweed natural product in the year 2000 prompted numerous chemical syntheses, including scalable preparations with as few as six‐steps. Herein we report the discovery and characterization of the concise two‐enzyme biosynthetic pathway to kainic acid from l‐glutamic acid and dimethylallyl pyrophosphate in red macroalgae and show that the biosynthetic genes are co‐clustered in genomes of Digenea simplex and Palmaria palmata. Moreover, we applied a key biosynthetic α‐ketoglutarate‐dependent dioxygenase enzyme in a biotransformation methodology to efficiently construct kainic acid on the gram scale. This study establishes both the feasibility of mining seaweed genomes for their biotechnological prowess.
- Subjects
BIOSYNTHESIS; NEUROCHEMISTRY; KAINIC acid; NEUROPHARMACOLOGY; GLUTAMATE receptors
- Publication
Angewandte Chemie, 2019, Vol 131, Issue 25, p8542
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201902910