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Abstract: The supply problem with regard to drug development and sustainable production lies in the limited amounts of biomass of most marine invertebrates available from wild stocks. Thus, most pharmacologically active marine natural products can only be isolated in minute yields. Total synthesis of pharmacologically active natural products has been successfully established but is in many cases economically not feasible due to the complexity of the molecular structures and the low yields. To solve the pressing supply issue in marine drug discovery, other strategies appear to be more promising. One of these is mariculture which has successfully been established with the bryozoan Bugula neritina (the source of the bryostatins) and the tunicate Ecteinascidia turbinata (the source of ET-743). Another strategy involves partial synthesis from precursors which are biotechnologically available. An example is ET-743 that can be partially synthesized from safracin B which is a metabolite of Pseudomonas fluorescens. There have been many examples of striking structural similarities between natural products obtained from marine invertebrates and those of microbial origin which suggests that microorganisms living in their invertebrate hosts could be the actual producers of these secondary metabolites. With regard to sustainable biotechnological production of pharmacologically important metabolites from marine invertebrates and their “endosymbionts”, a more advanced strategy is to focus on cloning and expression of the respective key biosynthetic gene clusters. This molecular biological approach will open up new avenues for biotechnological production of drugs or drug candidates from the sea.

Abstract: An investigation of the soft coral Asterospicularia laurae collected on the Great Barrier Reef, Australia, afforded the cytotoxic diterpene 13-epi-9-deacetoxyxenicin (1) in addition to the known metabolites 13-epi-9-deacetylxenicin (2) and gorgosterol. 13-Epi-9-deacetoxyxenicin readily underwent an autoxidation reaction in solution to afford a single product, the hydroperoxide 3. Structures, stereochemistry, and NMR assignments were established by high resolution NMR spectroscopy and by comparison with published data for known compounds.

Abstract: A new pyrrolopyrimidine alkaloid, rigidin E (1) and the known metabolites rigidin (2) and 1-methylherbipoline (3) have been isolated from a Papua New Guinea tunicate Eudistoma sp. A combination of spectroscopic data were used to determine the structures of these metabolites.

Abstract: CMP-Neu5Ac is an important sugar nucleotide for biosynthesis of sialic acid and its conjugates. In this paper, a large-scale production system of CMP-Neu5Ac by a single strain is reported. The co-expression of Neu5Ac aldolase (EC4.1.3.3) and CMP-Neu5Ac synthetase (EC 2.7.7.43) was achieved by constructing individual genes into one plasmid and having a single culture that has both NeuAc aldolase and CMP-Neu5Ac synthetase activities. Overall this system only employed N-acetylmannosamine, excess of pyruvate and CTP to produce CMP-Neu5Ac. This work has demonstrated that a large-scale synthesis of sialic acid-derived oligosaccharides could be achieved economically and efficiently through a single, biosynthetic pathway engineered microorganism.

Abstract: Two new long-chain C₃₃ polyacetylenic compounds, halicynones A and B were isolated from the marine sponge Haliclona sp. along with known analogs. The known compound pellynol A possessing a 1-yn-3-ol terminus, exhibited strong antitumor activity against the human colon tumor cell line HCT-116 (IC₅₀ 0.026 μg/mL), however, the corresponding 1-yn-3-one, halicynone A, was inactive, which suggests an important role for the terminal 1-yn-3-ol functional group in mediating cytotoxic activity.

Abstract: Putative precursors in pseudopterosin biosynthesis, the hydrocarbons isoelisabethatriene (10) and erogorgiaene (11), have been identified from an extract of Pseudopterogorgia elisabethae collected in the Florida Keys. Biosynthetic experiments designed to test the utilization of these compounds in pseudopterosin production revealed that erogorgiaene is transformed to pseudopterosins A-D. Together with our previous data, it is now apparent that early steps in pseudopterosin biosynthesis involve the cyclization of geranylgeranyl diphosphate to elisabethatriene followed by the dehydrogenation and aromatization to erogorgiaene.