Bathymetry 2500 5000 7500 11000 meters below sea level Fig.2 World ocean bathymetric map."The vast oceans cover 70%of the world's surface.with 95%greater than 1000 m deep species richness for many taxa of the Southern ocean compared both shallow and deep-water habitats.To the best of the his Arctic dthe nve natural product isolated to date from deep-sea fauna.The deep sea is variably defined as (>50 m)fauna dcfincd as thos inhabiting depths than so min order 3 Deep-sea life olves exposu to high cts inclu in this re requiring its inhabitants to mmercial iological proces tion.st the r region and metabolism and physiology. A number of deep-se because no such data have yet been reported. (cold-loving) and thermophilic heat-loving adapting to high pressure.and either cold temperatures (in 2 Reviews the majority of the deep sea or high temperatures (around Cold-water marine natural products isolated from organisms d ther re well b ucity of liter the ada collected from habitats below 4Cwere covered for the first time tation of marine invertebrates to deep-sea life.It is beyc in200 Caledon an marine cosystem the key that has ncluding deep-water sponges deep-watc nd Narral Producr 2001 Capon published ed b a minireview on natural products isolated from Australian She elhioetig ope from the Ryukyu Trench at a depth of 5110m. has revealed ch ab ssures abov Some of the col Isolation of th -B(17 acids (40-42 ase have reve 21 macrol A-E 122 ed that the expres sion of these components is pressure egulate A【er dase (d-type cyto chrome)in the resp B35 ting lipid membrane composition that it is This joumal isThe Royal Society of Chemistry 2008 Nat.Prod.Rep,2008.25.1131-116611133species richness for many taxa of the Southern ocean compared to the Arctic deep sea.7 This review describes the 390 novel natural products isolated to date from deep-sea fauna. The deep sea is variably defined as commencing at depths of anywhere between 100 and 1000 m;2 however, for the purposes of this review deep-sea fauna are defined as those inhabiting depths of greater than 50 m, in order to include those fauna beyond the depths of scuba. The majority of deep-sea natural products included in this review have been isolated from deep-sea sponges, echinoderms and microorgan￾isms obtained using manned submersibles, or from commercial and scientific dredging and trawling operations, and emanate from tropical, temperate and polar regions. Herein, where no biological activity is ascribed to a particular metabolite it is because no such data have yet been reported. 2 Reviews Cold-water marine natural products isolated from organisms collected from habitats below 4 C were covered for the first time in 2007 by Baker et al. in a review that included some deep-water examples.37, ‡ In 2004, Laurent and Pietra reviewed the natural product diversity of the New Caledonian marine ecosystem, including deep-water sponges.38 In 2001, a list of deep-water marine natural products appears in Pietra’s book Biodiversity and Natural Product Diversity. 39 In 2001, Capon published a minireview on natural products isolated from Australian marine sponges obtained from trawling operations.40 In 1998, Bewley and Faulkner reviewed lithistid sponge metabolites from both shallow and deep-water habitats.41 To the best of the author’s knowledge, this is the first comprehensive review to focus solely on marine natural products isolated from deep-sea (>50 m) fauna. 3 Deep-sea life Life in the deep sea involves exposure to high hydrostatic pressures and low temperatures, requiring its inhabitants to adapt their genetic, biochemical and physiological processes and presenting unique challenges in terms of gene regulation, struc￾ture and function of proteins and other cellular components, and metabolism and physiology.42,43 A number of deep-sea psychrophilic (cold-loving) and thermophilic (heat-loving) microorganisms have been isolated, and their mechanisms of adapting to high pressure,44–49 and either cold temperatures (in the majority of the deep sea)50–52 or high temperatures (around hydrothermal vents),21,53–55 have been well documented. In contrast, there is a paucity of literature surrounding the adap￾tation of marine invertebrates to deep-sea life. It is beyond the scope of this review to cover the diverse range of adaptive mechanisms reported for deep-sea fauna; however, some of the key data that has emerged regarding gene regulation, macromolecular structure and metabolism in the deep sea have been summarized below. Intense investigation into the piezophilic psychrophile Shewanella violacea, a bacterium isolated from deep-sea sediment from the Ryukyu Trench at a depth of 5110 m,56 has revealed much about its metabolic pathways. Shewanella violacea survives at atmospheric pressure, but as with several other piezophilic microorganisms, it shows enhanced growth at pressures above atmospheric pressure. Isolation of the genes encoding for the biosynthesis of a number of enzymes, including cytochromes (bd, cA, cB),57,58 glutamine synthetase,59 and RNA polymerase60 have revealed that the expression of these components is pressure￾regulated. A terminal oxidase (d-type cytochrome) in the respi￾ratory pathway of S. violacea is also expressed at high pressure, resulting in an altered lipid membrane composition that it is Fig. 2 World ocean bathymetric map.30 The vast oceans cover 70% of the world’s surface, with 95% greater than 1000 m deep. ‡ Some of the cold-water marine natural products reviewed by Baker et al.37 were isolated from deep-water habitats, and those compounds, paesslerins A–B (17–18), the 10-hydroxydocosapolyenoic acids (40–42), carolisterols A–C (66–68), guaymasol (108) and epiguaymasol (109), a cyclic tetrapeptide (111), streptokordin (112), g-indomycinone (113), caprolactins A–B (120–121), macrolactins A–F (122–129), (+)-formylanserinone B (135), ()-epoxyserinone A (136) and its enantiomer, hydroxymethylanserinone B (137) and deoxyanserinone B (138), have been included here for completeness. This journal is ª The Royal Society of Chemistry 2008 Nat. Prod. Rep., 2008, 25, 1131–1166 | 1133