Table 2.
Bioactive natural products and their putative origin identified in Heterobranch families that have representatives at BNP.
| Clade | Family | Species | Location | Chemistry | (Presumable) Origin of Compound | References |
|---|---|---|---|---|---|---|
| Anaspidae (sea hares) | Aplysiidae Lamarck, 1809 | Dolabella auricularia (Lightfoot, 1786) | Western Indian Ocean (Mauritius) | dolastatin 10 (1) | dietary (cyanobacteria) | [21] |
| Stylocheilus striatus (Quoy and Gaimard, 1832) | Australia (feeding study) | debromoaplysiatoxin (3), lyngbyatoxin A (6), | dietary (cyanobacteria Lyngbya majuscula) | [22,23,24,25,26,32,37] | ||
| Stylocheilus longicauda (Quoy and Gaimard, 1825) | not given, presumably Hawaii | aplysiatoxin (2), debromoaplysiatoxin (3) | dietary (cyanobacteria) | [22,23,24,25,26] | ||
| Stylocheilus longicauda (Quoy and Gaimard, 1825) | Black Point, Oahu, Hawaii | makalika ester (4), makalikone ester (5), lyngbyatoxin A acetate (7), malyngamide O (10) | dietary (cyanobacteria) | [27,28,29,30,31,35] | ||
| Stylocheilus longicauda (Quoy and Gaimard, 1825) | not given, presumably Hawaii | kulolide-1 (31) | dietary (cyanobacteria) | [63] | ||
| Bursatella leachii (Blainville, 1817) | Australia (feeding study) | lyngbyatoxin A (6) | dietary (cyanobacteria) | [37] | ||
| Sacoglossa | Caliphyllidae Tiberi, 1881 | Cyerce cristallina (Trinchese, 1881) | Mediterranean Sea | cyercene A 11) and B (12) and 1–5 (13–17) | de novo | [2,38] |
| Cyerce nigricans (Pease, 1866) | Lizard Island (Australia) | chlorodesmin (18) | diatery (green alga Chlorodesmis fastigiata) | [39,40] | ||
| Oxynoidae Stoliczka, 1868 (1847) | Lobiger serradifalci (Calcara, 1840) | Capo Miseno (Bay of Naples, Italy) | oxytoxin-1 (20) | modified from dietary caulerpynene (19) from green alga Caulerpa prolifera | [41,42,43] | |
| Oxynoe olivacea (Rafinesque, 1814) | Murcia (SE Spain) | oxytoxin-1 (20), oxytoxin-2 (21) | modified from dietary caulerpynene (19) from green alga Caulerpa prolifera | [41,42,43] | ||
| Oxynoe olivacea (Rafinesque, 1814) | Bay of Naples, Italy | oxytoxin-1 (20), oxytoxin-2 (21) | modified from dietary caulerpynene (19) from green alga Caulerpa prolifera | [41,42,43] | ||
| Plakobranchidae Gray, 1840 | Elysia chlorotica (Gould, 1870) | Bay of Fundy, Canada | elysione (22) | de novo | [3,51] | |
| Elysia viridis (Montagu, 1804) | Fusaro Lake, Bay of Naples, Italy | elysione (22) | de novo | [3,51] | ||
| Elysia translucens (Pruvot-Fol, 1957) | Capo Miseno, Bay of Naples, Italy | udoteal (23) | dietary from the green alga Udotea petiolata | [3,40] | ||
| Elysia halimedae (Macnae 1954) (accepted as Elysia pusilla (Bergh, 1871)) | Agat Bay, Guam | halimedatetracetate alcohol (25) | dietary (chemical modification of halimedatetraacetate (24) from Halimeda mucroloba Decaisne (Carlson and Hoff, 1978)) | [52] | ||
| Elysia rufescens (Pease, 1871) | Hawaii | kahalalide F (26) and isokahalalide F (27) | dietary (algae Bryopsis pennata; might be of bacterial origin, with Mycoplasma spp. and Vibrio spp. as possible producers) | [46,53,55,57] | ||
| Elysia ornata (Swainson, 1840) | coasts of Okha (India) | kahalalide F (26) and other kalahalides | dietary (algae Bryopsis pennata; might be of bacterial origin, with Mycoplasma spp. and Vibrio spp. as possible producers) | [46,48] | ||
| Elysia grandifolia (Kelaart, 1858) | Gulf of Mannar and Palk Bay, Rameswaram, India at 1 to 2 m depth. | kahalalide F (26) and other kalahalides | dietary (slugs were feeding on algae Bryopsis plumosa (Hudson); might be of bacterial origin, with Mycoplasma spp. and Vibrio spp. as possible producers) | [46,54] | ||
| Thuridilla hopei (Vérany, 1853) | Italy | thuridillins, e.g., thuridillin A (28) | de novo, with precursor derived from algae Pseudochlorodesmis furcellata (30) | [58,60] | ||
| Thuridilla splendens (Baba, 1949) | Australia | thuridillins | de novo, with precursor derived from algae P. furcellata 30) | [59,60] | ||
| Thuridilla hopei (Vérany, 1853) | Italy | thuridillin-related aldehydes, e.g., nor-thuridillinal (29) | de novo, with precursor derived from algae P. furcellata (30) | [58,60] | ||
| Cephalaspidea | Aglajidae Pilsbry, 1895 (1847) | Philinopsis speciosa (Pease, 1860) | Hawaii | Kulolide-1 (31), kulolide-2 (32), kulolide-3 (33), kulokainalide-1 (34), kulokahilide-1 (35), kulokahilide-1 (36) as well as tolytoxin 23-acetate (37) | dietary (cyanobacteria; transfer most likely mediated via herbivorous molluscs like Stylocheilus longicauda and Dolabella auricularia which in turn were readily accepted by P. speciosa in feeding experiment) | [61,62,63,64] |
| Navanax inermis (J. G. Cooper, 1862) | Pacific | navenones A-C (39-41), isopulo’upone (42), 5,6-dehydroaglajne-3 (43) | dietary (Bulla species, e.g., Bulla gouldiana) | [67,68,70] | ||
| Gastropteridae Swainson, 1840 | Sagaminopteron psychedelicum (Carlson and Hoff, 1974) | Guam | 3,5 dibromo-2-(2′,4′-dibromo-phenoxy)phenol (47) | dietary (sponge Dysidea granulosa) | [71,72] | |
| Sagaminopteron nigropunctatum (Carlson and Hoff, 1973) | Guam | 3,5 dibromo-2-(2′,4′-dibromo-phenoxy)phenol (47) | dietary (sponge Dysidea granulosa) | [71,73] | ||
| Haminoeidae Pilsbry, 1895 | Haminoea cyanomarginata (Heller and Thompson, 1983) | Gulf of Corinth (Greece) | brominated tetrahydropyran (48) | dietary (Western Australian sponge Haliclona sp. Grant, 1841) | [73] | |
| Haminoea cymbalum (Quoy and Gaimard, 1832) | Indian coasts | brominated tetrahydropyran (48) | dietary (sponge) | [73] | ||
| Haminoea cymbalum (Quoy and Gaimard, 1832) | Guam | kumepaloxane (49) | dietary (sponge) | [74] | ||
| Haminoea species | Naples (Italy) | haminol A–C (50–52), and haminol 1–6 (53–58 | de novo | [75,76] | ||
| Haminoea fusari (Alvarez, Garcia and Villani, 1993) | Naples (Italy) | polypropionates, haminol 1–6 (53–58) | de novo | [77] | ||
| Haminoea orbignyana (Férussac, 1822) | Naples (Italy) | haminol 1 and 2 (53–54) | de novo synthesis, shown by feeding study | [4] | ||
| Pleurobranchomorpha | Pleurobranchidae Gray, 1827 | Pleurobranchus forskalii (Rüppell and Leuckart, 1828) | Manado, Indonesia | keenamide A (59) | dietary (presumable cyanobacterial origin) | [78] |
| Pleurobranchus forskalii (Rüppell and Leuckart, 1828) | Ishigaki Island, Japan | cycloforskamide (60) | dietary (sponge with associated cyanobacteria) or symbiotic cyanobacteria | [79] | ||
| Pleurobranchus forskalii (Rüppell and Leuckart, 1828) | Ishigaki Island, Japan | ergosinine (61) | dietary (ascidian and/or endophytic fungi) | [81] | ||
| Pleurobranchus forskalii (Rüppell and Leuckart, 1828) | Philippines | chlorolissoclimide (62) and dichlorolissoclimide 63) | dietary (Lissoclinum species of ascidian) | [83,84] | ||
| Pleurobranchus. albiguttatus (Bergh, 1905) | Philippines | chlorolissoclimide (62), dichlorolissoclimide (63) and 3β-hydroxychlorolissoclimide (64) | dietary (Lissoclinum species of ascidian) | [83,84] | ||
| Nudibranchia Anthobranchia | Aegiridae P. Fischer, 1883 | Notodoris citrina (Bergh, 1875) | Gulf of Eilat, The Red Sea | naamidine A (65), isonaamidine-A (66) | dietary (sponge Leucetta chagosensis Dendy, 1913) | [85,86,87,88] |
| Notodoris gardineri (Eliot, 1906) | Philippines | isonaamidine-A (66), dorimidazole-A (67) | [88,89] | |||
| Notodoris gardineri (Eliot, 1906) | Great Barrier Reef | clathridine (68) | dietary (sponge) | [90,92,93] | ||
| Notodoris gardineri (Eliot, 1906) | Papua New Guinea | clathridine (68) | dietary (sponge Clathrina clathrus Schmidt, 1864) | [91,92,93] | ||
| Chromodorididae Bergh, 1891 | Ceratosoma amoenum (Cheeseman, 1886) | Great Barrier Reef | allolaurinterol (69) | dietary (origin could be red algae, e.g., of the genus Laurencia; 69 also found in cyanobacteria, via herbivorous sea slugs) | [94,95,96] | |
| Ceratosoma trilobatum (J.E. Gray, 1827) | South China Sea Coast | (−)-furodysinin (70) | dietary (sponge) | [97] | ||
| Ceratosoma gracillimum (Semper in Bergh, 1876) | South China Sea Coast | (−)-furodysinin (70) | dietary (sponge) | [97] | ||
| Ceratosoma gracillimum (Semper in Bergh, 1876) | South Coast of Hainan Island | (−)-furodysinin (70), nakafuran-9 (71) | dietary (sponge) | [97] | ||
| Chromodoris lochi (Rudman, 1982) | Fiji | latrunculin A (72) | dietary, 72 in Spongia (=Cacospongia) mycofijiensis, but could be produced by as yet uncultivated microorganism | [98,102] | ||
| Chromodoris lochi (Rudman, 1982) | Vanuatu | mycothiazole (74) | dietary, sponges, but could be produced by as yet uncultivated microorganism | [103,104] | ||
| Chromodoris lochi (Rudman, 1982) | Indonesia | laulimalide (syn fijianolide B) (75), isolaulimalide (syn fijianolide A) (76) | dietary, sponges, but could be produced by as yet uncultivated microorganism | [107,108,109] | ||
| Chromodoris hamiltoni (Rudman, 1977) | South Africa | Lantrunculin A (72) and B (73) | dietary (sponge) | [100,102] | ||
| Chromodoris elisabethina (Bergh, 1877) | Queensland, Australia | Lantrunculin A (72) and B (73) | dietary (sponge) | [101,102] | ||
| Chromodoris magnifica (Quoy and Gaimard, 1832) | Queensland, Australia | Lantrunculin A (72) and B (73) | dietary (sponge) | [101,102] | ||
| Chromodoris kuiteri (Rudman, 1982) | Queensland, Australia | Lantrunculin A (72) and B (73) | dietary (sponge) | [101,102] | ||
| Chromodoris annae (Bergh, 1877) | Queensland, Australia | Lantrunculin A (72) and B (73) | dietary (sponge) | [101,102] | ||
| Chromodoris quadricolor (Rüppell and Leuckart, 1830) | Red Sea | Lantrunculin A (72) and B (73) | dietary (sponge) | [101,102] | ||
| Chromodoris inorata (Pease, 1871) (accepted as Chromodoris aspersa (Gould, 1852)) | Japan | inorolide A (77), B (78), C (79) and various scalaranes | [110] | |||
| Chromodoris luteorosea (Rapp, 1827) (accepted as Felimida luteorosea (Rapp, 1827)) | Spain | norrisolide (80), polyrhaphin C (81), chelonaplysin C (82), luterosin (83), macfarlandin A (84), | dietary (sponge) | [111] | ||
| Chromodoris macfarlandi (Cockerell, 1901) (accepted as Felimida macfarlandi (Cockerell, 1901)) | California, USA | macfarlandines A–E (84–88) | dietary (sponge, structures related to compounds from Aplysilla sulphurea) | [111,112,113] | ||
| Chromodoris sinensis (Rudman, 1985) (accepted as Goniobranchus sinensis (Rudman, 1985)) | South China Sea | Aplyroseol-2 (89) | dietary (sponge, structures related to compounds from Aplysilla sp.) | [97] | ||
| Chromodoris reticulata (Quoy and Gaimard, 1832) (accepted as Goniobranchus reticulatus (Quoy and Gaimard, 1832)) | Australia | Aplyroseol-2 (89) and other diterpenes | dietary (sponge, structures related to compounds from Aplysilla sp.) | [115] | ||
| Chromodoris maridadilus (Rudman, 1977) (accepted as Hypselodoris maridadilus (Rudman, 1977)) | Hawaii | nakafuran-9 (71), nakafuran-8 (90) | dietary (sponge Dysidea fragilis) | [116] | ||
| Glossodoris atromarginata (Cuvier, 1804) (accepted as Doriprismatica stellata (Cuvier, 1804)) | Sri Lanka, Australia, India | furanoditerpenoid and scalarane type, structural variants of these metabolites (differences due to diff. sponge prey); spongiadiol (91), spongiadiol diacetate (92), epispongiadiol (93), 12-deacetoxy-12-oxodeoxoscalarin (94), heteronemin (95), mooloolabene D (96) | dietary (sponge, e.g., Spongia sp. (former Hyatella intestinales (Lamarck, 1814)), Hyrtios erectus (Keller, 1889) and Hyrtios sp.) | [117,118,119,120,121,122,123,124,125,126,127,128,129,130,131] | ||
| Glossodoris dalli (Bergh, 1879) (accepted as Felimida dalli (Bergh, 1879)) | Natural Park of Osa Ballena (Costa Rica) | homoscalarane and scalarane compounds | probably dietary from sponges | [132] | ||
| Glossodoris sedna (Ev. Marcus and Er. Marcus, 1967) (accepted as Doriprismatica sedna (Ev. Marcus and Er. Marcus, 1967)) | Natural Park of Osa Ballena (Costa Rica) | 12-deacetyl-23-acetoxy-20-methyl-12-episcalaradial (97) | probably dietary from sponges | [132] | ||
| Glossodoris rufomarginata (Bergh, 1890) | Hainan Island in the South China Sea | homoscalarane and scalarane compounds | probably dietary from sponges | [124] | ||
| Glossodoris pallida (Rüppell and Leuckart, 1830) | China and Guam | homoscalarane and scalarane compounds, different pattern at different location | probably dietary from sponges | [119] | ||
| Glossodoris vespa (Rudman, 1990) | Eastern Australia | homoscalarane and scalarane compounds | probably dietary from sponges | [119] | ||
| Glossodoris averni (Rudman, 1985) (accepted as Ardeadoris averni (Rudman, 1985)) | Eastern Australia | homoscalarane and scalarane compounds | probably dietary from sponges | [119] | ||
| Goniobranchus obsoletus (Rüppell and Leuckart, 1830) | Japan | most bioactive: dorisenones A (98), B (99), D (100), 11β-hydroxyspongi-12-en-16-one (101), spongian-16-one (102) | dietary (sponge Spongionella sp.) | [133] | ||
| Goniobranchus splendidus (Angas, 1864) | Australia | spongian-16-one (102), aplytandiene-3 (103), aplysulfurin (104) and aplyroseol-2 (89), the gracilins A (105), B (106), C (107), G (108), M (109)) | dietary (sponge Spongionella sp.) | [134,135,203] | ||
| Hypselodoris infucata (Rüppell and Leuckart, 1830) | Hawaii | nakafuran-8 (90) and nakafuran-9 (71) | dietary (sponge Dysidea fragilis (Montagu, 1814)) | [116,138] | ||
| Dendrodorididae O’Donoghue, 1924 (1864) | Dendrodoris limbata (Cuvier, 1804) | olepupuane (116) and polygodial (117) | de novo | [147,150,151,152] | ||
| Discodorididae Bergh, 1891 | Halgerda aurantiomaculata (Allan, 1932) | Japan, Australia | zooanemonin (118) and esmodil (119) | dietary (sponge, anemone Anemonia sulcate) | [153] | |
| Halgerda gunnessi Fahey and Gosliner, 2001 | Japan, Australia | investigated, but no compounds found | [153] | |||
| Halgerda rubicunda (Baba, 1949) (accepted as Sclerodoris rubicunda (Baba, 1949)) | Japan, Australia | investigated, but no compounds found | [153] | |||
| Halgerda theobroma (Fahey and Gosliner, 2001) | Japan, Australia | investigated, but no compounds found | [153] | |||
| Halgerda willeyi (Eliot, 1904) | Japan, Australia | investigated, but no compounds found | [153] | |||
| Paradoris indecora (Bergh, 1881) | Spain, Italy | variabilin (120) | dietary (sponge, e.g., Ircinia sp.) | [154] | ||
| Jorunna funebris (Kelaart, 1859) | India | jorumycin (121) | from structural similarity to ecteinascidin 743 (122) bacterial origin | [155,156,157] | ||
| Hexabranchidae Bergh, 1891 | Hexabranchus sanguineus (Rüppell and Leuckart, 1830) | Hawaii, Japan | Trisoxazole macrolides, i.e., ulapualide A (123) and B (124), halichondramides (126–129), kabiramide A–E (125, 130–133), | dietary, trisoxazole macrolides isolated from different sponges from the genera Halichondria, Mycale, Jaspis and Pachastrissa. halichondramides (126–129) isolated from sponge Halichondria sp. | [156,157,158,159,160,161,162,163,164,165,166,167,168] | |
| Phyllidiidae Rafinesque, 1814 | Phyllidia coelestis (Bergh, 1905) | Thailand | 1-formamido-10(1,2)-abeopupukeanane (134), 2-formamidopupukeanane (135) | dietary (sponge) | [176,177] | |
| Phyllidia ocellata (Cuvier, 1804) | Japan | cavernothiocyanate (136), 10α-isocyano-4-amorphene (137), axisonitrile-3 (138), and 7-isocyano-7,8-dihydro-α-bisabolene (139) | dietary ((136–139) from sponge Acanthella cf. cavernosa) | [179] | ||
| Phyllidia ocellata (Cuvier, 1804) | Australia | 2-isocyanoclovene (140), 2-isocyanoclovane (141), 1-isothiocyanatoepicaryolane (142), 4,5-epi-10-isocyanoisodauc-6-ene (143) | dietary (sponges) | [180] | ||
| Phyllidia varicosa (Lamarck, 1801) | Hawaii | 9-isocyanopupukeanane (144), 2-isocyanopupukeanane (145) | dietary, sponge Ciocalypta sp. (ex. Hymeniacidon sp.) | [182,183] | ||
| Phyllidia varicosa (Lamarck, 1801) | Indonesia | 9-isocyanopupukeanane (144), epimeric 9-thiocyanato-pupekeanane (147, 148) | dietary, sponge Ciocalypta sp. (ex. Hymeniacidon sp.) | [186] | ||
| Phyllidia varicosa (Lamarck, 1801) | Sri Lanka | 3-isocyanotheonellin (146) | dietary (sponge) | [185] | ||
| Phyllidiella rosans (Bergh, 1873) | Japan | 9-isocyanopupukeanane (144) | dietary (sponge) | [184] | ||
| Phyllidiella pustulosa (Cuvier, 1804) | Japan | axisonitrile-3 (138), unnamed molecule with isocyano group (155) and substituted axinisothiocyanate K derivative | dietary (sponge) | [190] | ||
| Phyllidiella pustulosa (Cuvier, 1804) | China | 3-isocyanotheonellin (146), amphilectene (152), kalihinol-A (153), kalihinol-E (154) | dietary (sponges, due to very similar compounds present in both samples) | [175] | ||
| Phyllidiella pustulosa (Cuvier, 1804) | Vietnam | 9-isocyanopupukeanane (144) and its C-9 epimer | dietary, based on the terpenes obtained the authors concluded that the mollusk feeds on sponges of the genera Acanthella, Halichondria, Axinella and Axinyssa | [189] | ||
| Phyllidiella pustulosa (Cuvier, 1804) | Fiji | axisonitrile-3 (138), 10-isothiocyano-4-cadinene (150)/10-thiocyanato-4-cadinene (151) | sponge Phakellia carduus, due to very similar secondary metabolites present in both samples | [187,188] | ||
| Polyceridae Alder and Hancock, 1845 | Tambja abdere (Farmer, 1978) | West coast of America | tambjamines A–D, tambjamines A (156), C (157) | dietary (bryozoan Sessibugula translucens) | [191] | |
| Tambja eliora (Er. Marcus and Ev. Marcus, 1967) | West coast of America | tambjamines A-D, tambjamines A (156), C (157) | dietary (bryozoan Sessibugula translucens) | [191] | ||
| Roboastra tigris (Farmer, 1978) | Gulf of California | tambjamines A-D, tambjamines A (156), C (157) | dietary (bryozoan Bugula neritida) | [191] | ||
| Nembrotha species | Micronesia | tambjamines A (156), C (157), E (158), F (159), the tambjamine aldehyde (160) and the blue tetrapyrrol (161) | dietary (ascidian Atapozoa sp.) | [138,192] | ||
| Nembrotha cristata (Bergh, 1877) | Ant Atoll | tambjamines A (156), C (157), E (158), F (159), the tambjamine aldehyde (160) and the blue tetrapyrrol (161) | dietary (ascidian Atapozoa sp.) | [138,192] | ||
| Nembrotha kubaryana (Bergh, 1877) | Sumilon Island, the Philippines | tambjamines C (157), E (158) and the blue tetrapyrrol (161) | dietary (ascidian Atapozoa sp.) | [138,192] | ||
| Nembrotha sp. | Apo Islands, the Philippines | tambjamines C (157), E (158), F (159), and the tambjamine aldehyde (160) | dietary (ascidian Atapozoa sp.) | [192] | ||
| Polycera atra (MacFarland, 1905) | Torrey Pines artificial reef | bryostatins, e.g., bryostatin 1 (162) | dietary (bryozoan Bugula neritina) | [193,194,195] | ||
| Subclade Cladobranchia | Facelinidae Bergh, 1889 | Phyllodesmium briareum (Bergh, 1896) | not known | brianthein W (110) and excavatolide C (111) | dietary (coral Briareum sp.) | [1] |
| Phyllodesmium magnum (Rudman, 1991) | not known | cembrane diterpenes, e.g., 11-episinulariolide acetate (112) | dietary, e.g., Sinularia spp., Capnella sp. | [1] | ||
| Flabellinidae Bergh, 1889 | Flabellina exoptata (Gosliner and Willan, 1991) | not known | hormarin (113) | dietary | [139,141] | |
| Flabellina ischitana (Hirano and Thompson, 1990) | not known | hormarin (113) | dietary | [139,141] | ||
| Flabellina pedata (Montagu, 1816) | not known | hormarin (113) | dietary | [139,141] | ||
| Flabellina affinis (Gmelin, 1791) | not known | hormarin (113) | dietary | [139,141] | ||
| Proctonotidae Gray, 1853 | Janolus cristatus (Delle Chiaje, 1841) | Mediterranean | janolusimide (114) | dietary (bryozoa) | [139,141] |