Bill Baker from the University of South Florida, Tampa, US, extols the virtues of cold-water marine natural products and considers their future prospects

The words coral and sponge might conjure up pleasant thoughts of warm tropical waters and colourful fishes.  The organic chemists among us may think of terpenes and polyketides, while pharmacologists might reflect on anti-inflammatory or anti-cancer agents.  That these disparate images are not incongruous is testament to the growing role of marine organisms as sources of biomedically important chemical diversity.  Yet much remains to be discovered.  With more than 70 per cent of the earth covered by oceans, marine natural products represent only 10 per cent of natural products described to date.  

Now modify that word association with the adjectives Antarctic, Arctic, or deep sea.  Thoughts of tropical islands flee, along with them chemical or biomedical connotations.  Icebergs, abyssal depths and sea water hovering within a few degrees of zero seem at first incompatible with corals and sponges, terpenes and polyketides, and the treatment of human disease.  And perhaps for good reason, as these extreme cold regions have traditionally been thought to be lacking in animal life and the accompanying ecological pressure to drive the evolution of chemical defenses.  Additionally, the cold-water diving, lack of diving support services and sheer remoteness of many of these habitats renders them difficult to rationalize as practical sources of biological or chemical diversity.

Nonetheless, accumulating biological and chemical research, points to a rich cold-water flora and fauna and an active ecology, as dependant upon chemical defenses as many lower latitude habitats.  Among bioactivity-producing organisms, sponge biodiversity in Antarctica is as high as that found at temperate latitudes, and deep sea microbial fauna are among the most diverse known.  Recent studies have also shown cold-water invertebrate-associated microbe communities are robust.   From the chemical laboratory, unique structural motifs have emerged, as have biological activity profiles that have caught the attention of the pharmaceutical industry.  Variolin B, for example, is a structurally unique cyclin-dependent kinase inhibitor from an Antarctic sponge that is in clinical development as an anti-cancer drug.  Meridianins and palmerolides derive from Antarctic tunicates and have advanced in synthetic and pharmacological studies.  Meridianins have a similar activity to variolin B, while palmerolide A, a potent inhibitor of the enzyme vacuolar-ATPase, targets melanoma.  In addition to cytotoxicity, cold-water natural products are known to act as antibiotic, antiviral, antifouling, hemolytic, serotonergic, and ion channel modulating agents, as well as displaying inhibitory activity toward a number of specific enzymes.

Besides the accumulating evidence for the biomedical potential of cold-water natural products, the statistics are also encouraging.  If the marine realm is largely understudied as a source of chemical diversity, the cold-water habitats are truly unstudied.  Consider that 90 per cent of the biosphere is marine, and that a significant portion of that habitat is found at the extreme low end of liquid water's temperature range, yet only 0.3 per cent of natural products reported to date have been isolated from species originating in these environments.

What's not to like about cold-water bioprospecting?  To be sure, these studies are difficult.  Diving under the ice is not your routine scuba diving operation and deep water habitats can only be sampled by ship-based equipment.   In polar regions, it is not unusual to have one to three meters of sea ice between diver and ocean, requiring extraordinary measures to gain access to the water.  Thermal gear, while quite satisfactory at keeping the diver warm, often weighs as much as, if not more, than the diver, rendering graceful egress from the water impossible.  Deep sea trawls, while less physically demanding than scuba diving, present mountains of fragrant biodiversity that must be sorted, often in difficult sea and weather conditions, and are environmentally damaging.  Further, while advances in sampling devices have made some deep sea sediments accessible, the abyss remains very difficult to sample.  

So the cold-water chemical diversity story has yet to unfold, but the case is compelling.  While sampling will always be more challenging in these environments, there is little doubt that chemical rewards of cold-water biodiversity await the intrepid bioprospector.  

Read Bill Bakers review on 'Cold-water marine natural products' in an upcoming issue of Natural Product Reports.