New Approaches to Detect Biosynthetic Gene Clusters in the Environment

Chen, Ray; Wong, Hon Lun; Burns, Brendan P.

doi:10.3390/medicines6010032

Cited by 36 publications

(43 citation statements)

References 60 publications

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“…Streptomyces sp. DSM 14386 produced five new compounds (17)(18)(19)(20)(21) in medium supplemented with 1.5% NaCl, while this strain produced two brominated congeners (22,23) in medium containing 1.5% NaBr [42]. Similarly, a novel antibacterial cyclodepsipeptide, named NC-1 (24), was produced by a red soil-derived strain Streptomyces sp.…”

Section: The Osmac Approach Mediated By Co-culturementioning

confidence: 99%

“…In addition, the advances in the studies of metabolism and metabolite profiling can also illustrate the entire network of metabolism and regulatory system contributing to biogenesis of the particular metabolite [19]. Thus, these multi-omics techniques have established a proper connection between genomic information, gene expression levels, and metabolism [20]. Thus, this knowledge provides new opportunities for discovering a larger diversity than those isolated to date [20,21].…”

Section: Introductionmentioning

confidence: 99%

“…Thus, these multi-omics techniques have established a proper connection between genomic information, gene expression levels, and metabolism [20]. Thus, this knowledge provides new opportunities for discovering a larger diversity than those isolated to date [20,21]. All this progress has resulted in the development of a powerful method for NPs discovery termed "genome mining".…”

Section: Introductionmentioning

confidence: 99%

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Recent Advances in Strategies for Activation and Discovery/Characterization of Cryptic Biosynthetic Gene Clusters in Streptomyces

et al. 2020

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Streptomyces spp. are prolific sources of valuable natural products (NPs) that are of great interest in pharmaceutical industries such as antibiotics, anticancer chemotherapeutics, immunosuppressants, etc. Approximately two-thirds of all known antibiotics are produced by actinomycetes, most predominantly by Streptomyces. Nevertheless, in recent years, the chances of the discovery of novel and bioactive compounds from Streptomyces have significantly declined. The major hindrance for obtaining such bioactive compounds from Streptomyces is that most of the compounds are not produced in significant titers, or the biosynthetic gene clusters (BGCs) are cryptic. The rapid development of genome sequencing has provided access to a tremendous number of NP-BGCs embedded in the microbial genomes. In addition, the studies of metabolomics provide a portfolio of entire metabolites produced from the strain of interest. Therefore, through the integrated approaches of different-omics techniques, the connection between gene expression and metabolism can be established. Hence, in this review we summarized recent advancements in strategies for activating cryptic BGCs in Streptomyces by utilizing diverse state-of-the-art techniques.

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Section: The Osmac Approach Mediated By Co-culturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Recent Advances in Strategies for Activation and Discovery/Characterization of Cryptic Biosynthetic Gene Clusters in Streptomyces

et al. 2020

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“…[5][6][7] Despite intensive studies, however, the full potential of microbes to produce natural products has not been realized. 8 Genome mining studies have shown that microbes encode many biosynthetic gene clusters (BGCs) that have not yet been characterized. 8 It is widely assumed that many of these clusters produce novel natural products and that further characterization of Streptomyces bacteria increases the probability of identifying molecules with unique chemical structures and new mechanisms of action.…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of Streptomyces bacteriophages and Streptomyces strains encoding biosynthetic arsenals: Streptomyces strains and phages for antibiotic discovery

Montaño¹,

Nideffer²,

Brumage³

et al. 2020

Preprint

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17 The threat to public health posed by drug-resistant bacteria is rapidly increasing, as some of 18 healthcare's most potent antibiotics are becoming obsolete. Approximately two-thirds of the 19 world's antibiotics are derived from natural products produced by Streptomyces encoded 20 biosynthetic gene clusters. Thus, in order to identify novel gene clusters, we sequenced the 21 genomes of four bioactive Streptomyces strains isolated from the soil in San Diego County and 22 used Bacterial Cytological Profiling adapted for agar plate culturing in order to examine the 23 mechanisms of bacterial inhibition exhibited by these strains. In the four strains, we identified 24 101 biosynthetic gene clusters. Some of these clusters were predicted to produce previously 25 studied antibiotics; however, the known mechanisms of these molecules could not fully account 26 for the antibacterial activity exhibited by the strains, suggesting that novel clusters might encode 27 antibiotics. When assessed for their ability to inhibit the growth of clinically isolated pathogens, 28 three Streptomyces strains demonstrated activity against methicillin-resistant Staphylococcus 29 aureus. Additionally, due to the utility of bacteriophages for genetically manipulating bacterial 30 strains via transduction, we also isolated four new phages (BartholomewSD, IceWarrior, Shawty, 31 and TrvxScott) against S. platensis. A genomic analysis of our phages revealed nearly 200 32 uncharacterized proteins, including a new site-specific serine integrase that could prove to be a 33 useful genetic tool. Sequence analysis of the Streptomyces strains identified CRISPR-Cas 34 systems and specific spacer sequences that allowed us to predict phage host ranges.35 Ultimately, this study identified Streptomyces strains with the potential to produce novel 36 chemical matter as well as integrase-encoding phages that could potentially be used to 37 manipulate these strains.38 Introduction 39 Antibiotic discovery is an international priority requiring immediate action. 1 The increasing 40 prevalence of multi-drug resistant (MDR) bacterial pathogens has resulted in an increased use 41 of last-resort antibiotics. [1][2][3] Microbes that produce natural products are the most prolific source 42 of clinically approved antibiotics. 4 In particular, soil dwelling Actinobacteria, notably 43 Streptomyces, account for two-thirds of the antibiotics currently on the market. 5-7 Despite 44 intensive studies, however, the full potential of microbes to produce natural products has not 45 been realized. 8 Genome mining studies have shown that microbes encode many biosynthetic 46 gene clusters (BGCs) that have not yet been characterized. 8 It is widely assumed that many of 47 these clusters produce novel natural products and that further characterization of Streptomyces 48 bacteria increases the probability of identifying molecules with unique chemical structures and 49 new mechanisms of action. 9 50 51 In addition to identifying Streptomyces strains containing potentially novel BG...

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“…The use of bioinformatics and omic workflow is a very recent approach in the effort to discover natural products in various environments, such as soils, aquatic environments, and microbial communities. Chen et al [31] present a literature review highlighting several methods, mainly bioinformatics, used to identify biosynthetic gene clusters that encode the biosynthesis of secondary metabolites in the environment, especially in environments where microorganisms are rarely cultivated. There are also several examples of how recent studies have explored the genetic basis for the synthesis of new natural products that have broad medical and industrial applications [31].…”

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confidence: 99%

Biological Potential and Medical Use of Secondary Metabolites

Seca

Pinto

2019

Medicines

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This Medicines special issue focuses on the great potential of secondary metabolites for therapeutic applications. The special issue contains 16 articles reporting relevant experimental results and overviews of bioactive secondary metabolites. Their biological effects and new methodologies that improve the lead compounds’ synthesis were also discussed. We would like to thank all 83 authors, from all over the world, for their valuable contributions to this special issue.

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New Approaches to Detect Biosynthetic Gene Clusters in the Environment

Cited by 36 publications

References 60 publications

Recent Advances in Strategies for Activation and Discovery/Characterization of Cryptic Biosynthetic Gene Clusters in Streptomyces

Recent Advances in Strategies for Activation and Discovery/Characterization of Cryptic Biosynthetic Gene Clusters in Streptomyces

Isolation and characterization of Streptomyces bacteriophages and Streptomyces strains encoding biosynthetic arsenals: Streptomyces strains and phages for antibiotic discovery

Biological Potential and Medical Use of Secondary Metabolites

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