Review Article Defensive Roles for Secondary Metabolites from Marine Sponges and Sponge-Feeding Nudibranchs

Tasieae, Vol. 32, No . 6, pp . 639-655, 1994 Elsevia Scirnex Ltd ~~-~1~1~94~E001~ Printed in Geest B~tain 0041-0101J94 526.00+ 0.00 REVIEW ARTICLE DEFENSIVE ROLES FOR SECONDARY METABOLITES FROM MARINE SPONGES AND SPONGE-FEEDING NUDIBRANCHS PeTEtt PRORSCH Julius-von-Sechs-Institut f'ttr Biowissenschaften, Universität Wiuzburg, Mittlerer Dallcnbelweg 64, D-97082 Wtitzburg, Germany (Received 19 November 1993 ; accepted 3 February 1994) P. PROKSCH. Defensive roles for secondary metabolites from marine sponges and sponge-feeding nudibranchs. Toxicon 32, 63955, 1994.-In the marine environment sponges (Porifera) constitute one of the most interesting sources of bioactive natural products. The high frequency of bioactive components in these primitive filter-feeders is interpreted as chemical defence of sponges against environmental stress factors such as predation, overgrowth by fouling organisms or competition for space. The highest incidence of toxic or deterrent sponge metabolites is consequently found in habitats such as coral reefs that are characterized by intense competition and feeding pressure due, for example, to carnivorous fish. Further support for the adaptive significance of sponge constituents is derived from the observation that sponges which are growing exposed are usually more toxic than those growing unexposed . Whereas the chemical defence of sponges seems to be highly effective against most species of fish, a group of shell-less gastropods, the nudibranchs, has specialized on sponges. While feeding on sponges the nudibranchs sequester the effective chemical armoury of their prey, which is subsequently employed for their own protection. Some nudibranchs, however, have become independent of this interspecific flow of natural products and are able to accumulate defensive compounds through de nova synthesis. INTRODUCTION Evarr though the search for bioactive natural products from marine organisms is still a young field when compared to the long tradition of terrestrial pharmacognosy, the last two or three decades of marine pharmacognosy have yielded a fascinating array of natural products with pronounced pharmacological activities, which in turn have prompted major screening efforts by academic institutions, pharmaceutical companies, and public health organizations such as the NCI, in the search for new drugs from the sea (e.g. voN BERr ePSCx, 1980; MUNRO et al., 1987; 1ZINEHART er al., 1993). Promising compounds that originated from these surveys include the powerful antitumour compounds didemnin B (1, Fig. 1) from tunicates of the genus Trididemntvn and bryostatin 1 (2, Fig. 1) from the bryozooan Bugula neritina (ScFnen-rz et al., 1993). Bryostatin 1 is expected to enter clinical 639 640 P. PROKSCH trials shortly (IREi,nxn et al., 1993). Other pharmacologically active marine natural products, such as tetrodotoxin (3, Fig. 1) or okadaic acid (4, Fig. 1), have been established as indispensable tools for physiological studies of Na+ channels (C.v and Joxnnrr, 1990) or of cellular processes involving phosphorylation and dephosphorylation (I'IAYSTEAD et al., 1989). Cli=OH Fya. 1 . C~c~u. srxucrux~s (Cwetinued ). 1, Dimemnin B; 2, bryostatin 1; 3, tetrodotoxin; 4, okadaic acid. Defensive Roles for Secondary Metabolites 641 CHO e H~C CH~ FhC CHs Z fl OH ~a. 1. S, Latrunculin-A; 6, latrunculin-B; 7, hetetonemin; 8, acalnr+cü~l: g, manoalide ; 10, seco-manoalide; 11, siphonodictidine . Marine invertebrates have yielded a larger number of bioactive natural products than algae haveIRELAND et al., 1993; FAULICIVER, 1993), which is in sharp contrast to the terrestrial envirotunent where plants are by far the richest source of secondary metabolites 642 P. PROKSCH NH OH Fya. 1. 12, Siphonodictyal-A; 13, aiphonodictyal-H ; 14, 1-methyladenine; I5, serothionin; _16, homoaerothionin ; 17, isofistularin-3 ; 18, acrophobin-2 . Defensive Roles for Secondary Metabolites 643 CN CONFIA CFI,OH F~c. 1 . l9, Fistularin-l ; 20, aeroplysinin-1 ; 21, dienone; 22, halichondrin-H ; 23, ciguatoxin . (Lucxrmt, 1984). Among the numerous groups of marine invertebrates the sponges (Porifera) and coelenterates (Coelenterata) are by far the leading sources of natural products in terms of the sheer number of compounds isolated (F~ul.xxeR, 1993). With regard to the biogenetic diversity of secondary constituents, sponges rank first. At least 644 P. PROKSCH 10(H1-1500 different natural products representing terpenoids, polyketides, and amino acid derivatives have been reported from sponges ~FALJLKNER, 1993 ; IRELAND et al., 1993 ; SARMA Bt al., 1993). H~C 24 2~ u H~ ÇHa H~C CH~ F~a. 1. 24, A diketopiperatine ; 25, 9-isocyanopupukeanane ; 26-_28, seaquiterpene and savterterpcne furane; 29-31, eeequiterpenéi~onitrilee, -isothiocyanates, and -formamide; 32, olepupuane . Defensive Roles for Secondary Metabolites 645 CHO H,C CFh FIaC CH~ Fta. 1 . 33, 7-Deaoetoxyolepupuane; 34, polygodial; 35, limatulone . The high incidence of bioactive natural products in sessile marine invertebrates, such as sponges that are frequently exposed to numerous stress factors such as predation, overgrowth by fouling organisms or competition for space without effective morphological defence mechanisms, is certainly not incidental. It is rather considered to have evolved as chemically mediated defence mechanisms protecting these soft-bodied invertebrates from environmental dangers. Research on the ecological importance of marine natural products is still in its infancy when compared to the long tradition of terrestrial chemical ecology which can be traced back at least 100 years (e.g. STAHL, 1904; ZuxnL, 1895). Ample experimental evidence in favour of the defensive role of secondary metabolites from sponges, however, already exists, although it is scattered in the literature. It is the aim of this report to compile this information and to give a comprehensive view of our current knowledge on the adaptive significance of secondary metabolites from sponges with other marine organisms. BIOLOGY OF SPONGES Sponges (Porifera) are primitive multicellular organisms that originated some 1 .6 billion years ago in the Paleozoic and are distinguished from the true Eumetazoa by the lack of organized tissues (Mïn.LER, 1982; $ARMA et al., 1993). All 5000 or so currently known sponge taxa are aquatic, with the majority of them restricted to the marine environment. Sponges are filter-feeders which inhale water through numerous pores (ostia) piercing the external body wall. These pores lead into a system of channels which, after permeating almost the whole body, open to the exterior by a few larger exhalant openings called oscula. A continual flow of water through this channel system is maintained by ciliary 646 P. PROKSCH action. From this stream of water microscopic food particles such as bacteria, microalgae or detritus are phagocytozed . Sponges show a circumpolar distribution and have adapted to a diverse array of marine habitats (MESS, 1989; SAxMA et al., 1993). They may be found beneath the antarctic ice-cover as well as in temperate or tropical oceans . The size, shape and colour of sponges may also vary extensively. Some species may reach a height of more than 2 m, whereas others can be found as tiny encrusting sponges on shells with diameters seldom exceeding more than a few centimeters. Some sponges are cryptic, living secluded in caves or niches, whereas others are found exposed, often signalling their presence by a bright and conspicuous coloration . Sponges contribute significantly to the biomass of most marine habitats, sometimes as dominant elements, for example on coral reefs (SARMA et al., 1993). In spite of their sessile existence, their longevity and their potential nutritional importance, sponges are only rarely attacked by predators such as carnivorous fish (BRAEKMAN and DALOZE, 1986; MESS, 1989). In a survey of the dietary habits of Caribbean reef fish only 11 out of a total of 200 different species analysed were found to feed on sponges, suggesting that sponges are avoided by the majority of the usually polyphagous reef fish (RANDALL and HARTMANN, 1968). Sponges in the classes Calcarea or Sclerospongiae may derive morphological protection from predators by their sharp silica or calcium carbonate spicules which are imbedded in the soft tissue. However, many sponges from the largest class Demospongiae, such as the bath sponge Spongia o~cinalis, have no morphological defence mechanisms since protective spicules are replaced by proteinaceous fibres made from spongin, which are unlikely to deter predators. Why are these seemingly defenceless sponges avoided by most marine predators? Chemical defence of marine sponges against fish Chemical defence through accumulation of sometimes copious quantities of toxic or deterrent natural products is commonly found within the Porifera (BRAEKMAN and DALOZE, 1986; MESS, 1989; PAwc.nc, 1993). A striking example of the significance of secondary products from sponges for the chemical defence against fish is provided by the vividly red-coloured sponge Latrunculia magn~ca that is found in the Gulf of Aquaba (Red Sea). Latrunculia magnfica is one of a few sponge species from this habitat that grow exposed, whereas the majority of sponges in the GulfofAquaba are cryptic and are usually found below coral growth or rocks (NEEMAN et al., 1975). Field observations indicated that specimens of L. magnifica were avoided by fish that readily accepted some of the cryptic sponges when exposed. When L. magnifica was squeezed, the sponge was found to

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