دورية أكاديمية
أعرض في EDS

Discovery, characterization, and engineering of an advantageous Streptomyces host for heterologous expression of natural product biosynthetic gene clusters.

التفاصيل البيبلوغرافية
العنوان: Discovery, characterization, and engineering of an advantageous Streptomyces host for heterologous expression of natural product biosynthetic gene clusters.
المؤلفون: Klumbys E; Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology, and Research (A*STAR), 31 Biopolis Way, #04-01, Nanos, Singapore, 138669, Republic of Singapore., Xu W; Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology, and Research (A*STAR), 31 Biopolis Way, #04-01, Nanos, Singapore, 138669, 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., 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., Wei Y; Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology, and Research (A*STAR), 31 Biopolis Way, #04-01, Nanos, Singapore, 138669, Republic of Singapore., Wong FT; 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.; 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., Zhao H; Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology, and Research (A*STAR), 31 Biopolis Way, #04-01, Nanos, Singapore, 138669, Republic of Singapore. zhao5@illinois.edu.; Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. zhao5@illinois.edu., Ang EL; Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology, and Research (A*STAR), 31 Biopolis Way, #04-01, Nanos, Singapore, 138669, Republic of Singapore. ang_ee_lui@sifbi.a-star.edu.sg.; 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. ang_ee_lui@sifbi.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. ang_ee_lui@sifbi.a-star.edu.sg.
المصدر: Microbial cell factories [Microb Cell Fact] 2024 May 24; Vol. 23 (1), pp. 149. Date of Electronic Publication: 2024 May 24.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101139812 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2859 (Electronic) Linking ISSN: 14752859 NLM ISO Abbreviation: Microb Cell Fact Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2002-
مواضيع طبية MeSH: Streptomyces*/genetics , Streptomyces*/metabolism , Multigene Family* , Biological Products*/metabolism , Polyketides*/metabolism , Metabolic Engineering*, Streptomyces coelicolor/genetics ; Streptomyces coelicolor/metabolism ; Streptomyces lividans/genetics ; Streptomyces lividans/metabolism ; Biosynthetic Pathways/genetics
مستخلص: Background: Streptomyces is renowned for its robust biosynthetic capacity in producing medically relevant natural products. However, the majority of natural products biosynthetic gene clusters (BGCs) either yield low amounts of natural products or remain cryptic under standard laboratory conditions. Various heterologous production hosts have been engineered to address these challenges, and yet the successful activation of BGCs has still been limited. In our search for a valuable addition to the heterologous host panel, we identified the strain Streptomyces sp. A4420, which exhibited rapid initial growth and a high metabolic capacity, prompting further exploration of its potential.
Results: We engineered a polyketide-focused chassis strain based on Streptomyces sp. A4420 (CH strain) by deleting 9 native polyketide BGCs. The resulting metabolically simplified organism exhibited consistent sporulation and growth, surpassing the performance of most existing Streptomyces based chassis strains in standard liquid growth media. Four distinct polyketide BGCs were chosen and expressed in various heterologous hosts, including the Streptomyces sp. A4420 wild-type and CH strains, alongside Streptomyces coelicolor M1152, Streptomyces lividans TK24, Streptomyces albus J1074, and Streptomyces venezuelae NRRL B-65442. Remarkably, only the Streptomyces sp. A4420 CH strain demonstrated the capability to produce all metabolites under every condition outperforming its parental strain and other tested organisms. To enhance visualization and comparison of the tested strains, we developed a matrix-like analysis involving 15 parameters. This comprehensive analysis unequivocally illustrated the significant potential of the new strain to become a popular heterologous host.
Conclusion: Our engineered Streptomyces sp. A4420 CH strain exhibits promising attributes for the heterologous expression of natural products with a focus on polyketides, offering an alternative choice in the arsenal of heterologous production strains. As genomics and cloning strategies progress, establishment of a diverse panel of heterologous production hosts will be crucial for expediting the discovery and production of medically relevant natural products derived from Streptomyces.
(© 2024. The Author(s).)
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معلومات مُعتمدة: NRF-CRP19-2017-05-00 National Research Foundation Singapore; NRF-CRP19-2017-05-00 National Research Foundation Singapore; NRF-CRP19-2017-05-00 National Research Foundation Singapore; NRF-CRP19-2017-05-00 National Research Foundation Singapore; NRF-CRP19-2017-05-00 National Research Foundation Singapore; NRF-CRP19-2017-05-00 National Research Foundation Singapore; C211917003 Agency for Science, Technology and Research
المشرفين على المادة: 0 (Biological Products)
0 (Polyketides)
SCR Organism: Streptomyces albus; Streptomyces venezuelae
تواريخ الأحداث: Date Created: 20240524 Date Completed: 20240525 Latest Revision: 20240527
رمز التحديث: 20240527
مُعرف محوري في PubMed: PMC11127301
DOI: 10.1186/s12934-024-02416-y
PMID: 38790014
قاعدة البيانات: MEDLINE
الوصف
تدمد:1475-2859
DOI:10.1186/s12934-024-02416-y