{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:58:30Z","timestamp":1785218310197,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100013254","name":"National College Students Innovation and Entrepreneurship Training Program","doi-asserted-by":"publisher","award":["202510316037Z"],"award-info":[{"award-number":["202510316037Z"]}],"id":[{"id":"10.13039\/501100013254","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973214"],"award-info":[{"award-number":["81973214"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["enviromicro-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microbial Biotechnology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Streptomyces<\/jats:italic>\n                    species are prolific sources of antimicrobials, yet their vast biosynthetic capacity remains underexploited due to the rediscovery of common antibiotics (e.g., ~1% for streptomycin and ~10% for streptothricin). To address this challenge, we developed a dual\u2010layer biosynthetic blockade system, designated CI\u2010ARS\n                    <jats:sup>3<\/jats:sup>\n                    , which integrates two orthogonal silencing modules: a competitive transcriptional silencer that represses transcription of the native biosynthetic gene cluster (BGC), and an antisense RNA\u2010based silencer that facilitates the degradation of BGC\u2010derived mRNAs and\/or translational inhibition. Implemented on a single\n                    <jats:italic>attB<\/jats:italic>\n                    site\u2013integrating plasmid (pSET152\u2010\n                    <jats:italic>aafssf<\/jats:italic>\n                    ) encoding both modules, CI\u2010ARS\n                    <jats:sup>3<\/jats:sup>\n                    robustly suppresses streptomycin and streptothricin biosynthesis across 54\n                    <jats:italic>Streptomyces<\/jats:italic>\n                    strains, achieving an inhibition efficiency of over 97% with high specificity for the target compounds under the tested conditions. The removal of these dominant backgrounds led to the discovery of enissomycin, a previously unreported antibacterial molecule. Enissomycin exhibited potent activity against\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                    <\/jats:styled-content>\n                    (MIC 4\u20138\u2009\u03bcg\/mL) and exhibited no significant cytotoxicity, highlighting its promise for drug development. Collectively, CI\u2010ARS\n                    <jats:sup>3<\/jats:sup>\n                    is a robust platform for the efficient dereplication of streptomycin and streptothricin, thereby expediting the discovery of novel antimicrobial compounds from\n                    <jats:italic>Streptomyces<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/1751-7915.70407","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:42:45Z","timestamp":1783921365000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Silencing of Aminoglycoside Biosynthesis for the Discovery of Novel Antimicrobials in\n                    <i>Streptomyces<\/i>"],"prefix":"10.1111","volume":"19","author":[{"given":"Yuncong","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Synthetic Biology, College of Life Sciences and Technology China Pharmaceutical University  Nanjing Jiangsu Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Synthetic Biology, College of Life Sciences and Technology China Pharmaceutical University  Nanjing Jiangsu Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Synthetic Biology, College of Life Sciences and Technology China Pharmaceutical University  Nanjing Jiangsu Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Synthetic Biology, College of Life Sciences and Technology China Pharmaceutical University  Nanjing Jiangsu Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenlin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Metabolomics Jiangsu Province Academy of Traditional Chinese Medicine  Nanjing Jiangsu Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jufen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Jiangbei Campus of The First Affiliated Hospital of Army Medical University  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Synthetic Biology, College of Life Sciences and Technology China Pharmaceutical University  Nanjing Jiangsu Province People's Republic of China"},{"name":"Laboratory of Chemical Biology, College of Life Sciences and Technology China Pharmaceutical University  Nanjing Jiangsu Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0778-4691","authenticated-orcid":false,"given":"Deli","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry China Pharmaceutical University  Nanjing Jiangsu Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0933-5902","authenticated-orcid":false,"given":"Xuri","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Synthetic Biology, College of Life Sciences and Technology China Pharmaceutical University  Nanjing Jiangsu Province People's Republic of China"},{"name":"Laboratory of Chemical Biology, College of Life Sciences and Technology China Pharmaceutical University  Nanjing Jiangsu Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.968053"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac556"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/417141a"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf334"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abo7793"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0241-9"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01141-y"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1030"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1039\/B603816F"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics14030222"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7NP00026J"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2019.10.008"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/1023666X.2011.620289"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-025-10797-5"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/tcr.201500210"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751-7915.70067"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3975"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.056"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07530-w"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-013-4504-2"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.632230"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751-7915.12716"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.5b00016"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-023-00993-0"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4NP00075G"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509638103"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4CS00238E"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00284-025-04237-7"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2023.102385"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03218-w"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751-7915.14541"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24119727"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(25)00118-5"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac60057a020"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1997.tb10339.x"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200801204"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.16.5595-5604.2005"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067509"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00985-13"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700556r"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11274-019-2789-4"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/jimb\/kuab017"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54196-z"}],"container-title":["Microbial Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1751-7915.70407","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1751-7915.70407","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1751-7915.70407","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:00:58Z","timestamp":1785214858000},"score":1,"resource":{"primary":{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/10.1111\/1751-7915.70407"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":43,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/1751-7915.70407"],"URL":"https:\/\/doi.org\/10.1111\/1751-7915.70407","archive":["Portico"],"relation":{},"ISSN":["1751-7915","1751-7915"],"issn-type":[{"value":"1751-7915","type":"print"},{"value":"1751-7915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-01-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70407"}}