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NCCOS Project

Characterization of Toxin Synthesis Pathways in Toxic Dinoflagellates

This project began in October 2005 and was completed in September 2015

During the past 25 years, the abundance, range, and variety of harmful algal blooms (HABs) and their toxins have been increasing, impacting human and marine animal health through consumption of contaminated shellfish, finfish, and water or aerosol exposure. HAB dinoflagellate algae make some of the most potent toxins on Earth, yet little is known about why or how they produce these compounds. Our objective is to understand the pathways by which toxins are produced in dinoflagellates.

Why We Care
Potent toxins produced by marine dinoflagellates cause more than 60,000 intoxication incidents per year with a 1.5 percent mortality rate, worldwide. The majority of dinoflagellate toxins adversely affecting human health are polyketides, natural organic compounds consisting of long carbon chains with oxygen-containing rings and synthesized by complex proteins known as polyketide synthases (PKS).

Identifying how these compounds are made in dinoflagellates will provide tools for understanding their regulation and function, monitoring toxin biosynthesis, and for implementing management strategies aimed at reducing human health impacts and local economies. Like bacterial PKS used to produce many antibiotics, dinoflagellate PKS may ultimately help develop therapeutics in human medicine.

What We Are Doing
Through DNA sequence analysis we identified several PKS genes in Karenia brevis, the Florida red tide dinoflagellate that produces brevetoxins. Characterization of these genes revealed that dinoflagellates possess novel PKS enzymes with an unprecedented structure. In K. brevis, the expression of these PKS enzymes differs in toxic and non-toxic cells, suggesting their involvement in toxin biosynthesis. We learned these enzymes are found in the chloroplast, the cell compartment responsible for photosynthesis. Our hypothesis is that PKS synthesizes the backbones for brevetoxin (called polyenes) in the chloroplast and then exports them to other cellular compartments for polyketide ring formation.

Next Steps
Moving on from identifying products of the PKS enzyme complex in K. brevis chloroplasts will involve new collaborations. In collaboration with an external partner, we initiated investigations into the location of the cyclization reactions. In collaboration with international partners, we are investigating the PKS enzymes in Ostreopsis and Coolia, two problematic dionflagellate HAB species in the Mediterranean Sea, and in the dinoflagellate Gambierdiscus, responsible for the most common form of seafood poisoning in the tropics, ciguatera fish poisoning.

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