Integrated Genomic and Metabolomic Approach to the Discovery of Potential Anti-Quorum Sensing Natural Products from Microbes Associated with Marine Samples from Singapore
Ji Fa Marshall Ong,
Hui Chin Goh,
Swee Cheng Lim,
Li Mei Pang,
Joyce Seow Fong Chin,
Koh Siang Tan,
Zhao-Xun Liang,
Liang Yang,
Evgenia Glukhov,
William H. Gerwick,
Lik Tong Tan
Affiliations
Ji Fa Marshall Ong
Natural Sciences and Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore 637616, Singapore
Hui Chin Goh
p53 Laboratory, Agency for Science, Technology and Research (A*STAR), #06-06, Immunos, 8A Biomedical Grove, Singapore 138648, Singapore
Swee Cheng Lim
St John’s Island National Marine Laboratory, Tropical Marine Science Institute, National University of Singapore, 18 Kent Ridge Road, Singapore 119227, Singapore
Li Mei Pang
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
Joyce Seow Fong Chin
Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
Koh Siang Tan
St John’s Island National Marine Laboratory, Tropical Marine Science Institute, National University of Singapore, 18 Kent Ridge Road, Singapore 119227, Singapore
Zhao-Xun Liang
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
Liang Yang
Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
Evgenia Glukhov
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USA
William H. Gerwick
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USA
Lik Tong Tan
Natural Sciences and Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore 637616, Singapore
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.
