Ana Catarina Guedes
DINOSSAUR: DINOflagellates for Sustained Supply of Active compoUnds in optimized photobioReactors
The long lasting interest on dinoflagellate microalgae for their being sources of marine biotoxins affecting seafood safety has boomed in recent years due to their unexpected application as pharmacological drugs. This is the case of Karlodinium genus, exhibiting the unique feature of synthesizing karlotoxins (with chemical structures recently resolved) with a noteworthy medical potential. Karlotoxins trigger formation of pores in cholesterol-containing cell membranes, thus disrupting osmotic balance and causing lysis; besides their obvious role as hypocholesterolemic pharmacore, karlotoxins may be used as antitumor agents. Therefore, our model biocatalyst and metabolite are well-defined – but the productivity of the latter is far from acceptable, thus constraining clinical testing and industrial production.
Large-scale chemical synthesis of karlotoxins is exceedingly complex; and the genome of their source dinoflagellates is unusually long and complex, thus hampering genetic and metabolic engineering. Culture in photobioreactors is thus the only realistic option to obtain significant quantities of those compounds. However, said microalgae are fragile and grow slowly, so classical (closed) photobioreactor configurations and operating conditions are not appropriate at all. Building on the somewhat scattered information on lab-scale cultivation of other dinoflagellates, novel photobioreactors will be designed, and operating conditions will be tuned – thus constituting the core innovation of this proposal.
In view of their great contribution to global processing costs in blue biotechnology, downstream separation techniques will also be addressed – toward novel solutions, or optimization of classical methods of harvesting, dehydration, and disruption of biomass, extraction, and purification of karlotoxins leached, and polishing of final commercial product. We will expand the existing portfolio of post-reactional handling methodologies – so as to develop dedicated techniques, suitable and optimized for a new class of compounds with pharmaceutical interest; and will assess the overall environmental impact and economic feasibility, after tentative scale up.