Abstract
The supply problem with regard to drug development and sustainable production lies in the limited amounts of biomass of most marine invertebrates available from wild stocks. Thus, most pharmacologically active marine natural products can only be isolated in minute yields. Total synthesis of pharmacologically active natural products has been successfully established but is in many cases economically not feasible due to the complexity of the molecular structures and the low yields. To solve the pressing supply issue in marine drug discovery, other strategies appear to be more promising. One of these is mariculture which has successfully been established with the bryozoan Bugula neritina (the source of the bryostatins) and the tunicate Ecteinascidia turbinata (the source of ET-743). Another strategy involves partial synthesis from precursors which are biotechnologically available. An example is ET-743 that can be partially synthesized from safracin B which is a metabolite of Pseudomonas fluorescens. There have been many examples of striking structural similarities between natural products obtained from marine invertebrates and those of microbial origin which suggests that microorganisms living in their invertebrate hosts could be the actual producers of these secondary metabolites. With regard to sustainable biotechnological production of pharmacologically important metabolites from marine invertebrates and their “endosymbionts”, a more advanced strategy is to focus on cloning and expression of the respective key biosynthetic gene clusters. This molecular biological approach will open up new avenues for biotechnological production of drugs or drug candidates from the sea.
Highlights
Among the various sources for the development of new drugs, compounds from living organisms, so called natural products, are of particular significance [1]
Recent examples of plant-derived anti-cancer drugs include paclitaxel from Taxus brevifolia, etoposide derived by partial synthesis from the lignan podophyllotoxin isolated from Podophyllum peltatum and irinotecan obtained based on the lead structure of camptothecin isolated from Camptotheca acuminata
It is no surprise that marine natural products have their stronghold in the area of anti-cancer chemotherapy as indicated by the list of compounds currently under clinical investigation [5]. Closer inspection of this list reveals that marine invertebrates such as sponges, tunicates, bryozoans and molluscs are the most interesting sources of pharmacologically active metabolites whereas for example seaweeds that grow so abundantly or other marine algae appear to be less promising in comparison
Summary
Among the various sources for the development of new drugs, compounds from living organisms, so called natural products, are of particular significance [1]. One third of todays best selling drugs are either natural products or have been developed based on lead structures provided by nature. Looking at drugs from nature it is surprising that up to now almost all medicinally used natural products or derivatives thereof were obtained from terrestrial organisms rather than from those inhabiting the sea. With regard to drug discovery and development, the oceans started to attract interest from pharmaceutical companies and research institutions only approximately 50 years ago with the discovery of the sponge-derived nucleosides spongothymidine and spongouridine [2] (Fig. 1). What are plausible reasons and obstacles that have slowed down marine drug development and what could be promising research avenues that will possibly provide solutions for the future?
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