دورية أكاديمية
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Exploring a general multi-pronged activation strategy for natural product discovery in Actinomycetes.

التفاصيل البيبلوغرافية
العنوان: Exploring a general multi-pronged activation strategy for natural product discovery in Actinomycetes.
المؤلفون: Tay DWP; Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science, Technology and Research (A*STAR), 8 Biomedical Grove, #07-01 Neuros Building, Singapore, 138665, Republic of Singapore., Tan LL; Molecular Engineering Lab, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, #07-06, Proteos, Singapore, 138673, Republic of Singapore., Heng E; Molecular Engineering Lab, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, #07-06, Proteos, Singapore, 138673, Republic of Singapore., Zulkarnain N; Molecular Engineering Lab, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, #07-06, Proteos, Singapore, 138673, Republic of Singapore., Ching KC; Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, #01-02, Nanos, Singapore, 138669, Republic of Singapore., Wibowo M; Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, #01-02, Nanos, Singapore, 138669, Republic of Singapore., Chin EJ; Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, #01-02, Nanos, Singapore, 138669, Republic of Singapore., Tan ZYQ; Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, #01-02, Nanos, Singapore, 138669, Republic of Singapore., Leong CY; Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, #01-02, Nanos, Singapore, 138669, Republic of Singapore., Ng VWP; Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, #01-02, Nanos, Singapore, 138669, Republic of Singapore., Yang LK; Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, #01-02, Nanos, Singapore, 138669, Republic of Singapore., Seow DCS; Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, #01-02, Nanos, Singapore, 138669, Republic of Singapore., Lim YW; Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science, Technology and Research (A*STAR), 8 Biomedical Grove, #07-01 Neuros Building, Singapore, 138665, Republic of Singapore., Koh W; Bioinformatics Institute (BII), Agency of Science, Technology and Research (A*STAR), 30 Biopolis Street, #07-01, Matrix, Singapore, 138671, Republic of Singapore., Koduru L; Molecular Engineering Lab, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, #07-06, Proteos, Singapore, 138673, Republic of Singapore., Kanagasundaram Y; Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, #01-02, Nanos, Singapore, 138669, Republic of Singapore., Ng SB; Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, #01-02, Nanos, Singapore, 138669, Republic of Singapore., Lim YH; Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science, Technology and Research (A*STAR), 8 Biomedical Grove, #07-01 Neuros Building, Singapore, 138665, Republic of Singapore. lim_yee_hwee@isce2.a-star.edu.sg.; Synthetic Biology Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore, 117597, Republic of Singapore. lim_yee_hwee@isce2.a-star.edu.sg., Wong FT; Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science, Technology and Research (A*STAR), 8 Biomedical Grove, #07-01 Neuros Building, Singapore, 138665, Republic of Singapore. wongft@imcb.a-star.edu.sg.; Molecular Engineering Lab, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, #07-06, Proteos, Singapore, 138673, Republic of Singapore. wongft@imcb.a-star.edu.sg.
المصدر: Communications biology [Commun Biol] 2024 Jan 06; Vol. 7 (1), pp. 50. Date of Electronic Publication: 2024 Jan 06.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]-
مواضيع طبية MeSH: Actinobacteria* , Biological Products*/pharmacology, Actinomyces ; Anti-Bacterial Agents/pharmacology ; Computational Biology
مستخلص: Natural products possess significant therapeutic potential but remain underutilized despite advances in genomics and bioinformatics. While there are approaches to activate and upregulate natural product biosynthesis in both native and heterologous microbial strains, a comprehensive strategy to elicit production of natural products as well as a generalizable and efficient method to interrogate diverse native strains collection, remains lacking. Here, we explore a flexible and robust integrase-mediated multi-pronged activation approach to reliably perturb and globally trigger antibiotics production in actinobacteria. Across 54 actinobacterial strains, our approach yielded 124 distinct activator-strain combinations which consistently outperform wild type. Our approach expands accessible metabolite space by nearly two-fold and increases selected metabolite yields by up to >200-fold, enabling discovery of Gram-negative bioactivity in tetramic acid analogs. We envision these findings as a gateway towards a more streamlined, accelerated, and scalable strategy to unlock the full potential of Nature's chemical repertoire.
(© 2024. The Author(s).)
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معلومات مُعتمدة: NRF-CRP19-2017-05-00 National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore); NRF-CRP19-2017-05-00 National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore); NRF-CRP19-2017-05-00 National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore); NRF-CRP19-2017-05-00 National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore); NRF-CRP19-2017-05-00 National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore); NRF-CRP19-2017-05-00 National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore); NRF-CRP19-2017-05-00 National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore); NRF-CRP19-2017-05-00 National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore); C211917006 Agency for Science, Technology and Research (A*STAR); C233017006 Agency for Science, Technology and Research (A*STAR); C211917003 Agency for Science, Technology and Research (A*STAR); C211917006 Agency for Science, Technology and Research (A*STAR); C233017006 Agency for Science, Technology and Research (A*STAR); C211917006 Agency for Science, Technology and Research (A*STAR)
المشرفين على المادة: 0 (Anti-Bacterial Agents)
0 (Biological Products)
تواريخ الأحداث: Date Created: 20240106 Date Completed: 20240108 Latest Revision: 20240202
رمز التحديث: 20240202
مُعرف محوري في PubMed: PMC10771470
DOI: 10.1038/s42003-023-05648-7
PMID: 38184720
قاعدة البيانات: MEDLINE
الوصف
تدمد:2399-3642
DOI:10.1038/s42003-023-05648-7