* Biotechnological potential of marine sponges and their associated bacteria as producers of new pharmaceuticals ( Part

Abstract

The examples of sponge-derived compounds in advanced stages of clinical trials presented in part I of this article emphasize the potential of sponges as auspicious source for drugs against various human diseases. However, compared to the vast number of over 4000 compounds isolated from sponges during the last three decades, the number of sponge-derived drugs that have already entered the market is surprisingly small. There are two major reasons for this phenomenon: One is the extremely long time frame involved in the process of drug development. For instance, to develop the famous anticancer drug Taxol® from its initial description in the yew tree to its approval as a commercial pharmaceutical took over 20 years. The presented examples of spongederived compounds in clinical trials, this long time frame is by far no exception. Thus, as many interesting compounds were initially reported already in the 1980s and early 1990s, there is hope that within the following years the number of commercially available ”marine drugs” will considerably increase. The second reason for the comparatively small number of sponge-derived drugs that are so far on the market is the fact that most pharmaceutically interesting natural products are available only in minute amounts from their natural sources, as they are present in sponge tissue in very low quantities. For structure elucidation, pharmaceutical and pharmacological assays and later on for clinical trials, however, considerable quantities of these compounds are needed. The lack of material is in fact the major limiting factor for the development of sponge-derived compounds to commercial drugs. Moreover, it has to be asked where the material for drug production should come from, in case the agent should really make it to the market. This problem is vividly illustrated by the example of the sponge-derived halichondrins (see part I). An annual need between 1 and 5 kg per year is estimated if these compounds should once be commercially available as anticancer drugs. If tissue of the sponge Lissodendoryx sp. was the only source of this material, this would mean harvesting 3,000–16,000 metric tonnes of sponge biomass per year. It is obvious that such large amounts could neither be taken from nature without risking extinction of the respective source species, nor could such an approach be at all economically feasible. Therefore, alternative strategies are needed to make sponge compounds better accessible for drug development. One solution may be chemical synthesis. Usually, once a new natural product has been discovered and there is proof for highly interesting pharmacological properties, many chemical labs all over the world quickly start attempts to synthesize it. However, natural products are often characterized by highly complex molecules, rendering their synthesis very labor intensive and thereby economically not feasible (especially when their fate in further clinical trials is precarious). Moreover, it has been shown that sometimes the synthetic products feature different pharmaceutical properties compared to their natural counterparts, even if all physicochemical measurements for both compounds are identical. Another possibility to provide higher amounts of a pharmaceutical relevant compound derived from marine invertebrates is mariculture, i.e., in-thesea cultivation of the source organism. This has proven fairly successful for the tunicate Ecteinascidia turbinata, which produces the anticancer drug ”Yondelis®” that is now in Phase III clinical trials conducted by the Spanish company PharmaMar and for the bryozoan Bugula neritina, source of the anticancer agent bryostatin 1, which is in Phase II clinical trials by GPC Biotech (Mendola 2000). The example of the abovementioned deep-water sponge Lissodendoryx sp. that still produces halichondrins when cultivated in shallow-water is promising as well. The obtained compound yields, however, are still far from those that will be needed once one of these compounds has finally entered the market. Moreover, mariculture does not afford complete Carsten Thoms*/Peter Schupp*

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@inproceedings{Thoms2003BP, title={* Biotechnological potential of marine sponges and their associated bacteria as producers of new pharmaceuticals ( Part}, author={Carsten Thoms and Peter J. Schupp}, year={2003} }