Scalable Biosynthesis of the Seaweed Neurochemical, Kainic Acid.

Authors:
Jonathan R Chekan
Jonathan R Chekan
University of Illinois at Urbana-Champaign
United States
Malia L Moore
Malia L Moore
Drug Information Center
Little Rock | United States
Shane G Poplawski
Shane G Poplawski
The State University of New York
United States

Angew Chem Int Ed Engl 2019 Apr 17. Epub 2019 Apr 17.

Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, 92093, USA.

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.

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http://doi.wiley.com/10.1002/anie.201902910
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http://dx.doi.org/10.1002/anie.201902910DOI Listing
April 2019
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