Abstract
Representatives of the genus Streptomyces from terrestrial sources have been the focus of intensive research for the last four decades because of their prolific production of chemically diverse and biologically important compounds. However, metabolite research from this ecological niche had declined significantly in the past years because of the rediscovery of the same bioactive compounds and redundancy of the sample strains. More recently, a new picture has begun to emerge in which marine-derived Streptomyces bacteria have become the latest hot spot as new source for unique and biologically active compounds. Here, we investigated the marine sediments collected in the temperate cold waters from British Columbia, Canada as a valuable source for new groups of marine-derived Streptomyces with antimicrobial activities. We performed culture dependent isolation from 49 marine sediments samples and obtained 186 Streptomyces isolates, 47 of which exhibited antimicrobial activities. Phylogenetic analyses of the active isolates resulted in the identification of four different clusters of bioactive Streptomyces including a cluster with isolates that appear to represent novel species. Moreover, we explored whether these marine-derived Streptomyces produce new secondary metabolites with antimicrobial properties. Chemical analyses revealed structurally diverse secondary metabolites, including four new antibacterial novobiocin analogues. We conducted structure-activity relationships (SAR) studies of these novobiocin analogues against methicillin-resistant Staphylococcus aureus (MRSA). In this study, we revealed the importance of carbamoyl and OMe moieties at positions 3” and 4” of novobiose as well as the hydrogen substituent at position 5 of hydroxybenzoate ring for the anti-MRSA activity. Changes in the substituents at these positions dramatically impede or completely eliminate the inhibitory activity of novobiocins against MRSA.
Highlights
The discovery of new bioactive natural products from marine sources has become an important research area due to the extraordinary chemical diversity and novelty found in marine natural products and their potential applications as lead compounds in drug development [1,2]
The world’s oceans provide the largest habitat for microorganisms on earth and they are the home to diverse uncharacterized microbial communities
In response to the challenge and crisis of widespread antibiotic resistance, we have examined marine sediments collected in the cold/temperate waters of Georgia Strait, Bamfield, Howe Sound, and Indian Arm, British Columbia, Canada as a source for new groups of marine-derived Streptomyces with antimicrobial activities
Summary
The discovery of new bioactive natural products from marine sources has become an important research area due to the extraordinary chemical diversity and novelty found in marine natural products and their potential applications as lead compounds in drug development [1,2]. The ocean covers approximately 70% of the Earth’s surface and has the potential to provide a treasure trove of largely unexplored biodiversity. In the past 30 years, bioprospecting for new marine natural products has yielded several thousand chemically diverse compounds [3]; in 2009 to 2010 alone 2,014 novel marine natural products were discovered [4,5]. The world’s oceans provide the largest habitat for microorganisms on earth and they are the home to diverse uncharacterized microbial communities
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