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|Title:||Bioprospecting indigenous actinomycetes for natural product discovery||Authors:||Pang, Li Mei||Keywords:||DRNTU::Science::Biological sciences||Issue Date:||2018||Source:||Pang, L. M. (2018). Bioprospecting indigenous actinomycetes for natural product discovery. Doctoral thesis, Nanyang Technological University, Singapore.||Abstract:||Actinomycetes are well-known prolific producers of bioactive secondary metabolites, including some most effective antibiotics in use today. The secondary metabolites isolated from actinomycetes accounts for 45% of natural product derived antimicrobial drugs. After the golden era of antibiotic discovery from 1940s to 1960s, the “Waksman platform” faced diminished returns. The rapid emergence of antimicrobial resistance among many pathogenic bacteria creates an urgent need for more potent antimicrobial compounds to fill the drug pipeline. Many researchers have ventured into underexplored environments to search for novels strains that has potential of producing novel compounds with interesting bioactivities. Little information is currently available for actinomycetes biodiversity in ecologically interesting sites in Singapore. The Sungei Buloh Wetland Reserve (SBWR) and Pulau Ubin Quarry Lake are considered to be unique in biotas because of different environmental conditions such as pressures, nutrient compositions and temperatures. In my Ph.D. research, I aimed to isolate unique actinomycetes strains from the two locations for the discovery of novel biosynthetic pathways and antimicrobial secondary metabolites. To uncover novel actinomycetes, I employed a variety of media recipes and in situ cultivation methods in the isolation processes, which yielded a total of 152 actinomycetes strains. The highest number of actinobacteria were found to be affiliated with the genus Streptomyces, followed by Micromonospora, Verrucosispora, Jishengella, Pseudonocardia, Isoptericola, Mycobacterium and Microbacterium. More than two third of the strains were tested to be bioactive against one or more clinical isolates such as Methicillin-resistant Staphylococcus aureus (MRSA). Taking advantage of the falling cost of genome sequencing, we performed genome sequencing and metabolite profiling to further prioritize the strains to identify the strains that have the highest potential to produce novel compounds. Several “high-potential” strains were identified based on the bioactivity assay, genome sequence and metabolite profiling results. We isolated and characterized two bioactive compounds from two such high-potential strains. While the first bioactive compound produced by Streptomyces sp. P19 is the known antimicrobial compound echinomycin, the second compound 4’,5-dihydroxy-7-methoxy-3-methylflavanone produced by Streptomyces sp. SD50 is a new compound and is a potent agonist of estrogenic receptor. We believe that many more novel biosynthetic pathways and microbial secondary metabolites will be uncovered from the high-potential strains identified by my research work. Hence, the research work described in the dissertation sets the stage for the downstream discovery of novel microbial natural products.||URI:||http://hdl.handle.net/10356/75687||DOI:||10.32657/10356/75687||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
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