Tan, Lik Tong

In the past year (July 2014 to March 2015), 90 secondary school students participated in an Environmental Science themed Project-Based Learning (PBL) program designed by scientists at the National Institute of Education, Singapore. The authenticity of the PBL program was enhanced by partnership with NParks' Coastal Biomonitoring program. A total of 22 school teachers were also involved as facilitators of their students' project work. The strategic partnership of NIE scientists, secondary schools and NParks created a unique experience for students engaging in PBL.

Three new cyanobactins, trikoramides B (1)–D (3), have been isolated from the marine cyanobacterium, Symploca hydnoides, following a preliminary bioassay-guided isolation of the two most active polar fractions based on the brine shrimp toxicity assay. These new cyanobactins are new analogues of the previously reported cytotoxic trikoramide A (4) with differences mainly in the C-prenylated cyclotryptophan unit. Their planar structures were elucidated from their 1D and 2D NMR spectral data in combination with the HRMS/MS data. Marfey’s method, 2D NOESY NMR spectroscopic and ECD spectra analyses were used to determine the absolute stereochemistry of trikoramides B (1)–D (3). Trikoramides B (1) and D (3) exhibited cytotoxicity against MOLT-4 acute lymphoblastic leukemia cell line with IC50 values of 5.2 µM and 4.7 µM, respectively. Compounds 1 and 3 were also evaluated for their quorum-sensing inhibitory assay based on the Pseudomonas aeruginosa PAO1 lasB-gfp and rhlA-gfp bioreporter strains. Although trikoramide B (1) exhibited weak quorum-sensing inhibitory activity, the Br-containing trikoramide D (3) exhibited moderate to significant dose-dependent quorum-sensing inhibitory activities against PAO1 lasB-gpf and rhlA-gfp bioreporter strains with IC50 values of 19.6 µM and 7.3 µM, respectively.

Diverse ecologically important metabolites, such as allelochemicals, infochemicals and volatile organic chemicals, are involved in marine organismal interactions. Chemically mediated interactions between intra- and interspecific organisms can have a significant impact on community organization, population structure and ecosystem functioning. Advances in analytical techniques, microscopy and genomics are providing insights on the chemistry and functional roles of the metabolites involved in such interactions. This review highlights the targeted translational value of several marine chemical ecology-driven research studies and their impact on the sustainable discovery of novel therapeutic agents. These chemical ecology-based approaches include activated defense, allelochemicals arising from organismal interactions, spatio-temporal variations of allelochemicals and phylogeny-based approaches. In addition, innovative analytical techniques used in the mapping of surface metabolites as well as in metabolite translocation within marine holobionts are summarized. Chemical information related to the maintenance of the marine symbioses and biosyntheses of specialized compounds can be harnessed for biomedical applications, particularly in microbial fermentation and compound production. Furthermore, the impact of climate change on the chemical ecology of marine organisms—especially on the production, functionality and perception of allelochemicals—and its implications on drug discovery efforts will be presented.

With 70% of the Earth’s surface covered in water, the marine ecosystem offers immense opportunities for drug discovery and development. Due to the decreasing rate of novel natural product discovery from terrestrial sources in recent years, many researchers are beginning to look seaward for breakthroughs in new therapeutic agents. As part of an ongoing marine drug discovery programme in Singapore, an integrated approach of combining metabolomic and genomic techniques were initiated for uncovering novel anti-quorum sensing molecules from bacteria associated with subtidal samples collected in the Singapore Strait. Based on the culture-dependent method, a total of 102 marine bacteria strains were isolated and the identities of selected strains were established based on their 16S rRNA gene sequences. About 5% of the marine bacterial organic extracts showed quorum sensing inhibitory (QSI) activity in a dose-dependent manner based on the Pseudomonas aeruginosa QS reporter system. In addition, the extracts were subjected to mass spectrometry-based molecular networking and the genome of selected strains were analysed for known as well as new biosynthetic gene clusters. This study revealed that using integrated techniques, coupled with biological assays, can provide an effective and rapid prioritization of marine bacterial strains for downstream large-scale culturing for the purpose of isolation and structural elucidation of novel bioactive compounds.

Microorganisms play a significant role in biofouling and biocorrosion within the maritime industry. Addressing these challenges requires an innovative and integrated approach utilizing marine natural products with beneficial properties. A comprehensive screening of 173 non-toxic EtOAc and H₂O extracts derived from diverse marine organisms collected in Indonesian waters was conducted using a robust panel of assays. These included antimicrobial tests and classical biosurfactant assays (drop collapse and oil displacement), as well as anti-quorum-sensing (QS) and anti-biofilm assays. These screening efforts identified five active extracts with promising activities. Among these, EtOAc extracts of the marine tunicate Sigilina cf. signifera (0159-22e) and the marine sponge Lamellodysidea herbacea (0194-24c) demonstrated significant anti-biofouling activity against Perna indica and anti-biocorrosion performance (mpy 10.70 ± 0.70 for S. cf. signifera; 7.87 ± 0.86 for L. herbacea; 13.60 ± 1.70 for positive control Tetracorr CI-2915). Further chemical analyses of the active extracts, including LC-HR-MS/MS, MS-based molecular networking, and chemoinformatics, revealed the presence of both known and new bioactive compounds. These included tambjamines and polybrominated diphenyl ethers (PBDEs), which are likely contributors to the observed bioactivities. Subsequent investigations uncovered new anti-QS and anti-biofilm properties in synthetic and natural PBDEs 1–12 previously derived from L. herbacea. Among these, 8 exhibited the most potent anti-QS activity, with an IC50 value of 15 µM, while 4 significantly reduced biofilm formation at a concentration of 1 µM. This study highlights the potential of marine-derived compounds in addressing biofouling and biocorrosion challenges in a sustainable and effective manner.

Theβ-hydroxyl amino acid unit is a common structural feature of many bioactive marine cyanobacterial depsipeptides. In this study, the absolute stereochemistry of the β-hydroxyl acid moieties in hantupeptins and trungapeptins were determined through their synthesis and HPLC analysis of the Mosher ester derivatives. Synthesis of two3-hydroxy-2-methyloctanoic acid (Hmoa) stereoisomers, (2S,3R)-Hmoa and (2S,3S)-Hmoa, were achieved using diastereoselective asymmetric method and the retention times of all four Hmoa isomers were established indirectly by RPLC-MS analysis of their Mosher ester derivative standards. Based on the retention times of the standards, the absolute configuration of the Hmoa unit in hantupeptin C (3) and trungapeptin C (6) was assigned as (2R,3S)- and (2S,3R)-Hmoa, respectively. The use of the Mosher's reagents, coupled with HPLC analysis, provided a viable alternative to the absolute stereochemical determination of -hydroxy acid units in depsipeptides.

The prokaryotic filamentous marine cyanobacteria are photosynthetic microbes that are found in diverse marine habitats, ranging from epiphytic to endolithic communities. Their successful colonization in nature is largely attributed to genetic diversity as well as the production of ecologically important natural products. These cyanobacterial natural products are also a source of potential drug leads for the development of therapeutic agents used in the treatment of diseases, such as cancer, parasitic infections and inflammation. Major sources of these biomedically important natural compounds are found predominately from marine cyanobacterial orders Oscillatoriales, Nostocales, Chroococcales and Synechococcales. Moreover, technological advances in genomic and metabolomics approaches, such as mass spectrometry and NMR spectroscopy, revealed that marine cyanobacteria are a treasure trove of structurally unique natural products. The high potency of a number of natural products are due to their specific interference with validated drug targets, such as proteasomes, proteases, histone deacetylases, microtubules, actin filaments and membrane receptors/channels. In this review, the chemistry and biology of selected potent cyanobacterial compounds as well as their synthetic analogues are presented based on their molecular targets. These molecules are discussed to reflect current research trends in drug discovery from marine cyanobacterial natural products.

A new cyclic decapeptide, trikoramide A (1), has been isolated from samples of the marine cyanobacterium Symploca hydnoides, collected from Bintan Island, Indonesia. Trikoramide A (1) is a C-prenylated cyclotryptophan-containing cyanobactin. Its planar structure was deduced by 1D and 2D NMR spectroscopy as well as HR–MS/MS data. In addition, its absolute configuration was determined by Marfey’s method and 2D NOESY NMR spectroscopic analysis. Compound 1 possessed cytotoxicity against the MOLT-4 and AML2 cancer cell lines with IC50 values of 4.8 and 8.2 μM, respectively.