Mariculture and Natural Production of the Antitumoural (+)-Discodermolide by the Caribbean Marine Sponge Discodermia dissoluta

Abstract

Biotechnological research on marine organisms, such as ex situ or in situ aquaculture and in vitro cell culture, is being conducted to produce bioactive metabolites for biomedical and industrial uses. The Caribbean marine sponge Discodermia dissoluta is the source of (+)-discodermolide, a potent antitumoural polyketide that has reached clinical trials. This sponge usually lives at depths greater than 30 m, but at Santa Marta (Colombia) there is a shallower population, which has made it logistically possible to investigate for the first time, on ways to supply discodermolide. We thus performed in situ, 6-month fragment culture trials to assess the performance of this sponge in terms of growth and additional discodermolide production and studied possible factors that influence the variability of discodermolide concentrations in the wild. Sponge fragments cultured in soft mesh bags suspended from horizontal lines showed high survivorship (93 %), moderate growth (28 % increase in volume) and an overall rise (33 %) in the discodermolide concentration, equivalent to average additional production of 8 μg of compound per millilitre of sponge. The concentration of discodermolide in wild sponges ranged from 8 to 40 μg mL(-1). Locality was the only factor related to discodermolide variation in the wild, and there were greater concentrations in peripheral vs. basal portions of the sponge, and in clean vs. fouled individuals. As natural growth and regeneration rates can be higher than culture growth rates, there is room for improving techniques to sustainably produce discodermolide.

Recent progress with microtubule stabilizers: new compounds, binding modes and cellular activities

“…40 Improvements in aquaculture show that D. dissolute can be successfully cultivated from sponge fragments and discodermolide yield improved. 41 Discodermolide’s chemical structure consists of a flexible chain that can adopt infinite numbers of conformations both in solution and with tubulin. In fact, a study by the Horwitz laboratory using hydrogen deuterium exchange showed that unlike paclitaxel, which interacts mainly with the M-loop of tubulin, discodermolide orients towards the N-terminal H1-S2-loop.…”

Marine Microorganism-Invertebrate Assemblages: Perspectives to Solve the “Supply Problem” in the Initial Steps of Drug Discovery

“…While sea-based culture techniques (Figure 2) have proven to be feasible for products, such as halichondrin [70], avarol [61] and discodermolide [71], ex situ approaches have not yet been very successful, mostly due to the lack of scientific knowledge on sponge biology. Sponges have a high potential for growth, but release most of their productivity through the shedding of cellular materials into the environment [72,73,74,75,76].…”

“…A clear genotype-associated difference in performance ( i.e. , growth and metabolite production) was observed for Discodermia dissoluta [71]. Such genotypic differences suggest that broodstock optimization through genotypic selection can help increase sponge mariculture productivity.…”

“…Most sponges in mariculture retain their ability to produce the compound of interest [49,50,71,77,78,79]. Cultured explants of Discodermia dissoluta even contained higher amounts of discodermolide than their wild conspecifics [71].…”

“…Cultured explants of Discodermia dissoluta even contained higher amounts of discodermolide than their wild conspecifics [71]. Attempts to enhance secondary metabolism in mariculture included stress treatments, which were successfully applied to increase the production of avarol [80] and latrunculin B [81].…”