Bioassay guided fractionation of a crude extract of the marine sponge Neopetrosia exigua resulted in the first reported isolation of exiguamines A and B. These pyrroloquinone alkaloids have an unprecedented hexacyclic skeleton that has not been previously encountered in natural products. Biological studies have identified exiguamine A as a potent in vitro inhibitor of the enzyme indoleamine-2,3-dioxygenase (IDO). IDO is an enzyme expressed by tumor cells to evade the immune system. Inhibitors against this enzyme may allow the immune system to attack cancer cells, making this enzyme a potential drug target for anti-cancer agents. Investigation of the crude extract of a Bacillus sp. collected in Dominica led to the isolation of the known diketopiperazine cyclo(S-Val-S-Phe) (3.9). In vitro biological studies revealed that cyclo(S-Val-S-Phe) is able to promote neurite outgrowth, even in the presence of physiological inhibitors. In vivo studies have shown that cyclo(S-VaI-S-Phe) is able promote sprouting in serotonergic and adrenergic axons. Synthesis of the other three diastereomers led to the discovery that cyclo(R-Val-R-Phe) is also an in vitro activator of axonal outgrowth. Inhibitors of the G2 checkpoint are able to increase the cytotoxicity of DNA damaging chemotherapeutics. Bioassay guided fractionation of an extract of the South American plant Duguetia odorata led to the isolation of the G2 checkpoint abrogator, oliveroline. This investigation also led to the isolation of the previously unreported alkaloid N-methylguatterine, and the known alkaloids dehydrodiscretine and pseudopalmatine. Chemical investigation of the marine sponge Myrmekioderma granulatum led to the isolation of the new compounds abolenone and myrmekioside C, as well as the known compounds curcudiol, curcuphenol, abolene and sesquiterpenoid. Biological studies of these compounds revealed that curcudiol is a ligand of the sex hormone-binding globulin. This protein is involved in transporting and regulating the concentration of steroids such as testosterone and estradiol. Many pathological conditions have a lower plasma concentration of these steroids. Ligands to SHBG can release steroids into the blood, so this protein is a potential drug target to treat conditions where a hormone insufficiency is present. / Science, Faculty of / Chemistry, Department of / Graduate

A 4.6-fold increase in the bimass of Cliona delitrix infesting Montastrea cavernosa substrate occurred in a portion of the Grand Cayman fringing reef affected by the discharge of untreated fecal sewage.It is suggested that the 6.3-fold increase in bacteria biomass (both coliforms and natural marine bacterioplankton) is linked to the sponge proliferation at the polluted site. Since demosponges normally obtain much of their nutritional needs from URPOC and only 11 from bacteria, the significance of the elevated bacteria count may be limited to its importance as a flag as an indicator of untreated sewage effluent. At the polluted study site, Montastrea cavernosa exhibited a 451 reduction in the amount of substrate occupied by living polyps.The loss of this respiring coral biomass is probably not compensated for by the biomass increases of C. delitrix and of the microflora inhabiting the dead substrate.The increased C. delitrix biomass reflects a. similar increase in the amount of M. cavernosa skeleton that has been eroded and reduced to silt-sized sediment. Thus, the discharge of untreated sewage into the reef environment can have a profound effect upon the trophic distribution of reef fauna, leading to a disturbance of the precarious balance between carbonate production and destruction on the reef. / Thesis / Bachelor of Science (BSc)

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Natural products continue to be a valuable source of compounds in research involving chemical ecology and drug discovery. Secondary metabolites are biosynthesized to benefit the host organism in its environment (feeding deterrence from predators, antibiotic properties to avoid infection, etc.) but these compounds also serve as useful scaffolds in drug discovery applications. The research herein describes both aspects of these two branches of natural products chemistry. The Antarctic sponge Dendrilla membranosa produces diterpenes, of which membranolide A, deters feeding of the predatory amphipod Gondogenia antarctica. A metabolomic study of several sponges was undertaken to determine environmental factors that govern the metabolism of D. membranosa. Habitat specificity, above or below the algal canopy, was a significant factor for the chemical clustering of sponges as well as the abundance of potential amphipod predators that are prevalent within the canopy. Another D. membranosa diterpene, aplysulphurin, undergoes degradation upon methanolic treatment to form the methoxy membranolides B-H. An investigation of these artifacts reveals potent activity against the leishmaniasis-causing parasite Leishmania donovani. Microorganisms also generate a significant number of bioactive natural products. Biotic and abiotic culture stressors such as co-culturing and epigenetic modification, respectively, will be explored to turn on cryptic biosynthetic pathways. These techniques are shown to produce unique secondary metabolites from cultures and further reinforce the one strain many compounds approach to the versatile and formidable microbial domain.

Terpios hoshinota is coral-killing sponge which grows and covers most stony corals in shallow waters. It was first discovered at Green Island in 2006, and have since killed a lot of coral, yet we know little about the physiology of Terpios hoshinota. This research focuses on the propagation and growth of the sponge. In the sexual reproduction part, we collected tissue samples in 2009 and 2010, the sperm cells were found only in Jun and Aug in 2009. The oocytes were found in Apr, Jul, and Aug. In 2010, embryos occurred. No lunar pattern was found in a high-frequency sampling of tissues comparing the occurrence and sizes of oocytes and embryos. Embryos are more likely to be found in the central part of the sponge; this pattern does not apply to oocytes nor to sperm cells. The sponge may be hermaphroditic male and female gametes are developed at different locations or times. The sponge fragments can reinfect new host corals, although such capability decreased with increasing number of days suspending in the water column. The spicules parallel to each other and to the growth axis in tissue threads, moreover, the sponge quickly extended numerous tissue threads in the absence of adequate coral substrate, which may serve the function of reaching new hosts. The sponge grows faster under light than under dimmed conditions. Fusion of tissues could occur between non-identical genotypes, and allografting pairs of tissues have higher rates of rejection than isografting pairs. After allografting the sponge fragments from different areas, the fusion rates were depended on the distance of two populations in the northern coast of Green Island. The results supported that self-seeding is the mechanism how Terpios hoshinota populations exploded in the north coast Green Island. The ability to cross to the neighboring corals, to propagate by fragments, and to produce embryos may have all contributed to their self-seeding capability.

Terpios hoshinota is a blackish-gray cyanobacteriosponge encrusting on stony corals with fast expansion rates in shallow waters. The sponge population exploded at Green Island and Orchid Island during 2006 to 2008. Here, we surveyed at Green Island and Orchid Island in 2009 and 2010, compared the sponge densities, individual lengths, sponge coverage and scleractinian coral coverage between 2008 and 2010. We also tested the hypothesis that typhoon may play a role inhibiting the sponges by monitoring individual sponges before and after. In these three years, the sponge coverages remained the same; sponge length and densities had no significant difference at 2~3 m depth at Green Island, but densities decreased and length increase at 5 m depth at Green Island and 2~3 m depth at Orchid Island, but the rate increased was significant slower than average growth speed . Although sponge coverages were not significant different between these years, the scleractinian corals coverages decreased at Green Island among these years. The main wind direction was southwest during the Typhoon Marakot at Green Island, and only the sponges at southwest coast of Green Island decreased in size significantly among the three coasts monitored. The population of Sponge T. hoshinota exploded in 2006, the strength of typhoons were smaller than other years during 2005 to 2009. The typhoon may be the main factor that inhibiting the sponge T. hoshinota at these two islands.

In the study on the chemical constituents from the Formosan marine organisms, four steroids, including three cholanic acid type metabolites, deoxycholic acid 3,12-diacetate (1), deoxycholic acid 3,12-diacetate-24-methyl ester (2), 3£\,7£\,12£\-triacetoxy-5£]-cholanic acid (3), and a principal steroid, gorgosterol (4), were isolated from the soft coral Klyxum simplex, collected at southern Taiwan coast. The structures of steroids 1-4, were elucidated by extensive spectroscopic methods, particularly in 1D and 2D NMR experiments. To best of our knowledge, there is no report on the isolation of cholanic acid type steroids from any marine source. Based on detailed analysis, steroid 2 was found to be a new natural product and this is the first time to isolate steroid 1 from natural resource. Furthermore, two known isoquinoline quinones, mimosamycin (5) and O-demethylrenierone (6) and a known steroid,24,28-didehydroaplysterol (7), were obtained from an Indonesian sponge belonging to the genus Halichondria (Halichondriidae). The structures of metabolites 5-7 were determined by spectral data analysis and by comparison with the spectral and physical data of other known compounds. The antimicrobial activity of compounds 1-7 against Staphylococcus aureus were assayed. It was found that compounds 1, 5 and 6 showed antimicr- obical activity toward Staphylococcus aureus.

The sponge Cinachyrella australiensis (Demospongiae: Spirophorida) is widely distributed in Indian ocean, West Pacific ocean, and Australian waters. It also can be found in the intertidal pools of Wun-Li-Ton in southern Taiwan. The sponge can propagate asexually by budding. According to the previous studies, this sponge was suspected to be symbiotic with sulfur-oxidizing chemoautotrophic bacteria. How the generation do obtain this symbiont is still unknow. In this study, PCR was used to amplify the DNA extracted from buds and sponges to obtained the 16S rDNAs. A total of 20 clones from each bud and mature sponge samples were randomly selected and sequenced. The results indicated that the major symbiotic bacteria constitute 65¢H of the clones derived form the mature sponge and 15¢H from the buds. The dominant symbionts contain RubisCO gene and are related to the sulfur-oxidizing chemoautotrophic bacteria, associated with the tube worms of the deep sea hydrothermal vents. The location of the sulfur-oxidizing chemoautotrophic bacteria was observed by fluorescence in situ hybridization (FISH). It was found that the sulfur-oxidizing chemoautotrophic bacteria were intracellular symbiosis within the cells of cortex, archaeocytes of mesoglial, and bud. Similar results were also observed at the junction of a developing bud and mature sponge. Apparently, the symbionts are transmitted from sponge to bud vertically. Furthermore, in this study, we also found several other intracelluar symbionts besides the major symbiotic bacterium,some of them are autotrophic in nature.