دورية أكاديمية
Synergy between Genome Mining, Metabolomics, and Bioinformatics Uncovers Antibacterial Chlorinated Carbazole Alkaloids and Their Biosynthetic Gene Cluster from Streptomyces tubbatahanensis sp. nov., a Novel Actinomycete Isolated from Sulu Sea, Philippines.
| العنوان: | Synergy between Genome Mining, Metabolomics, and Bioinformatics Uncovers Antibacterial Chlorinated Carbazole Alkaloids and Their Biosynthetic Gene Cluster from Streptomyces tubbatahanensis sp. nov., a Novel Actinomycete Isolated from Sulu Sea, Philippines. |
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| المؤلفون: | Tenebro CP; Center for Chemical Biology and Biotechnology, University of San Agustin, Iloilo City, Philippines., Trono DJVL; Center for Chemical Biology and Biotechnology, University of San Agustin, Iloilo City, Philippines., Balida LAP; Center for Chemical Biology and Biotechnology, University of San Agustin, Iloilo City, Philippines., Bayog LKA; Center for Chemical Biology and Biotechnology, University of San Agustin, Iloilo City, Philippines., Bruna JR; Center for Chemical Biology and Biotechnology, University of San Agustin, Iloilo City, Philippines., Sabido EM; Center for Chemical Biology and Biotechnology, University of San Agustin, Iloilo City, Philippines., Caspe DPC; Center for Natural Drug Discovery and Development, University of San Agustin, Iloilo City, Philippines., de Los Santos ELC; Research Analytics, Early Solutions Data & Translational Services, UCB Celltech, Slough, Berkshire, United Kingdom.; Balik Scientist Program, Department of Science and Technology, Philippine Council for Health Research and Development, Bicutan, Taguig City, Philippines., Saludes JP; Center for Natural Drug Discovery and Development, University of San Agustin, Iloilo City, Philippines.; Balik Scientist Program, Department of Science and Technology, Philippine Council for Health Research and Development, Bicutan, Taguig City, Philippines.; Department of Chemistry, College of Liberal Arts, Sciences, and Education, University of San Agustin, Iloilo City, Philippines., Dalisay DS; Center for Chemical Biology and Biotechnology, University of San Agustin, Iloilo City, Philippines.; Balik Scientist Program, Department of Science and Technology, Philippine Council for Health Research and Development, Bicutan, Taguig City, Philippines.; Department of Biology, College of Liberal Arts, Sciences, and Education, University of San Agustin, Iloilo City, Philippines. |
| المصدر: | Microbiology spectrum [Microbiol Spectr] 2023 Feb 21, pp. e0366122. Date of Electronic Publication: 2023 Feb 21. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: ASM Press Country of Publication: United States NLM ID: 101634614 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2165-0497 (Electronic) Linking ISSN: 21650497 NLM ISO Abbreviation: Microbiol Spectr Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : ASM Press, 2013- |
| مستخلص: | In this study, a novel actinomycete strain, DSD3025 T , isolated from the underexplored marine sediments in Tubbataha Reefs Natural Park, Sulu Sea, Philippines, with the proposed name Streptomyces tubbatahanensis sp. nov., was described using polyphasic approaches and characterized using whole-genome sequencing. Its specialized metabolites were profiled using mass spectrometry and nuclear magnetic resonance analyses, followed by antibacterial, anticancer, and toxicity screening. The S. tubbatahanensis DSD3025 T genome was comprised of 7.76 Mbp with a 72.3% G+C content. The average nucleotide identity and digital DNA-DNA hybridization values were 96.5% and 64.1%, respectively, compared with its closest related species, thus delineating the novelty of Streptomyces species. The genome encoded 29 putative biosynthetic gene clusters (BGCs), including a BGC region containing tryptophan halogenase and its associated flavin reductase, which were not found in its close Streptomyces relatives. The metabolite profiling unfolded six rare halogenated carbazole alkaloids, with chlocarbazomycin A as the major compound. A biosynthetic pathway for chlocarbazomycin A was proposed using genome mining, metabolomics, and bioinformatics platforms. Chlocarbazomycin A produced by S. tubbatahanensis DSD3025 T has antibacterial activities against Staphylococcus aureus ATCC BAA-44 and Streptococcus pyogenes and showed antiproliferative activity against colon (HCT-116) and ovarian (A2780) human cancer cell lines. Chlocarbazomycin A exhibited no toxicity to liver cells but moderate and high toxicity to kidney and cardiac cell lines, respectively. IMPORTANCE Streptomyces tubbatahanensis DSD3025 T is a novel actinomycete with antibiotic and anticancer activities from Tubbataha Reefs Natural Park, a United Nations Educational, Scientific and Cultural Organization World Heritage Site in Sulu Sea and considered one of the Philippines' oldest and most-well-protected marine ecosystems. In silico genome mining tools were used to identify putative BGCs that led to the discovery of genes involved in the production of halogenated carbazole alkaloids and new natural products. By integrating bioinformatics-driven genome mining and metabolomics, we unearthed the hidden biosynthetic richness and mined the associated chemical entities from the novel Streptomyces species. The bioprospecting of novel Streptomyces species from marine sediments of underexplored ecological niches serves as an important source of antibiotic and anticancer drug leads with unique chemical scaffolds. |
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| فهرسة مساهمة: | Keywords: Streptomyces; antibiotic; anticancer; biosynthetic gene clusters; flavin reductase; halogenated carbazole alkaloids; specialized metabolites; tryptophan halogenase |
| تواريخ الأحداث: | Date Created: 20230222 Latest Revision: 20240216 |
| رمز التحديث: | 20240216 |
| مُعرف محوري في PubMed: | PMC10100901 |
| DOI: | 10.1128/spectrum.03661-22 |
| PMID: | 36809153 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2165-0497 |
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| DOI: | 10.1128/spectrum.03661-22 |