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Biological and metabolomic approaches to drug discovery from microbes associated with deep water marine samples from Singapore
Author
Ong, Marshall Ji Fa
Supervisor
Tan, Lik Tong
Abstract
Marine sponges are one of the oldest multicellular metazoan to have survived through several major climatic changes throughout its 600 million years history. They are one of the most efficient sessile filter feeders, which harbor a myriad of microbes that could represent an enormous potential source of pharmaceutical agents. The diversity of microbes found within these sponge tissues can sometime far exceed those that are present in their surrounding seawater by as much as two to three folds.
The aim of the study is to expedite the discovery of novel marine bacterial secondary metabolites for drug discovery efforts without wasting resources on rediscovery of known compounds. Both biological as well as metabolomics approaches, such as the Mass Spectrometry (MS)-based molecular networking, were used in this study on selected marine bacteria associated with deep water marine specimens, mainly sponges, collected at the Singapore Straits. A total of 102 marine bacterial strains were isolated using the culture-dependent method and some of their identities were established based on their 16S rRNA gene sequences. Five marine bacterial organic extracts showed activity (dose-dependent inhibition for five bacterial extracts) based on the Pseudomonas aeruginosa quorum sensing inhibition (PaQSI) assay. In addition, six bacterial extracts showed more than 80% toxicity when tested at 1000ppm in the brine shrimp toxicity (BST) bioassay. The MS-based molecular networking approach was then used to screen these bioassay positive marine bacterial extracts for the presence of known or related bioactive natural products. Such extracts would not be of interest in our study as we aim to isolate bioactive compounds that are structurally novel in nature. The molecular networking technique was particularly useful as a dereplication tool in the selection of marine bacterial strains for downstream large-scale fermentation for the purpose of chemical elucidation. This study had revealed the biotechnological potential of our isolated marine bacteria associated with deep-water samples in our drug discovery and development efforts.
The aim of the study is to expedite the discovery of novel marine bacterial secondary metabolites for drug discovery efforts without wasting resources on rediscovery of known compounds. Both biological as well as metabolomics approaches, such as the Mass Spectrometry (MS)-based molecular networking, were used in this study on selected marine bacteria associated with deep water marine specimens, mainly sponges, collected at the Singapore Straits. A total of 102 marine bacterial strains were isolated using the culture-dependent method and some of their identities were established based on their 16S rRNA gene sequences. Five marine bacterial organic extracts showed activity (dose-dependent inhibition for five bacterial extracts) based on the Pseudomonas aeruginosa quorum sensing inhibition (PaQSI) assay. In addition, six bacterial extracts showed more than 80% toxicity when tested at 1000ppm in the brine shrimp toxicity (BST) bioassay. The MS-based molecular networking approach was then used to screen these bioassay positive marine bacterial extracts for the presence of known or related bioactive natural products. Such extracts would not be of interest in our study as we aim to isolate bioactive compounds that are structurally novel in nature. The molecular networking technique was particularly useful as a dereplication tool in the selection of marine bacterial strains for downstream large-scale fermentation for the purpose of chemical elucidation. This study had revealed the biotechnological potential of our isolated marine bacteria associated with deep-water samples in our drug discovery and development efforts.
Date Issued
2018
Call Number
QR106 Ong
Date Submitted
2018