{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:09:25Z","timestamp":1788768565011,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"50","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Nonribosomal peptide (NRP) antibiotics exhibit potent biological activities and are broadly used in clinical therapy. Because most microorganisms are difficult to culture and many antibiotic biosynthetic genes are silent, traditional activity tracking approaches face major limitations in the discovery of novel NRPs. Here, based on a synthetic bioinformatic natural product (syn\u2010BNP) discovery approach that integrates bioinformatics and chemical synthesis, a novel nonribosomal peptide synthetase (NRPS) gene cluster from the genome of\n                    <jats:italic>Rhodococcus erythropolis<\/jats:italic>\n                    D\u20101 was mined. A putative NRP scaffold synthesized by the NRPS encoded by this cluster was predicted. Through chemical synthesis and four rounds of structure\u2010activity relationship (SAR) studies, 37 NRP analogs were ultimately generated. Among these analogs, ZURJC28 shows activity against multiple Gram\u2010positive bacteria, including two drug\u2010resistant strains. Mechanistic studies and metabolomics analyses revealed that ZURJC28 exerts membrane\u2010disruptive activity associated with interaction with phosphatidylglycerol (PG)\u2010enriched Gram\u2010positive membranes, leading to membrane damage and widespread metabolic dysregulation. ZURJC28 also shows low cytotoxicity and low hemolytic activity, suggesting its preliminary in vitro safety profile.\n                  <\/jats:p>","DOI":"10.1002\/advs.76103","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T08:25:20Z","timestamp":1781166320000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of a Nonribosomal Peptide Analog With Activity Against Multiple Gram\u2010Positive Bacteria via a Synthetic Bioinformatic Natural Product Discovery Approach"],"prefix":"10.1002","volume":"13","author":[{"given":"Keyi","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Biochemistry College of Life Sciences Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Liang","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry College of Life Sciences Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry College of Life Sciences Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianan","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry College of Life Sciences Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry College of Life Sciences Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenguang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry College of Life Sciences Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry College of Life Sciences Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjie","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry College of Life Sciences Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyue","family":"Wang","sequence":"additional","affiliation":[{"name":"Liangzhu Laboratory Zhejiang University Medical Center  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4534-1322","authenticated-orcid":false,"given":"Hui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry College of Life Sciences Zhejiang University  Hangzhou China"},{"name":"ZJU\u2010UoE Joint Research Centre for Engineering Biology International Campus of Zhejiang University Zhejiang University  Haining China"},{"name":"Zhejiang University\u2010Lishui Joint Innovation Center for Life and Health &amp; Lishui Lvgu Institute for Life and Health  Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469\u20100691.2011.03570.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00181\u201019"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00284\u2010020\u201002197\u20108"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.blo.0000175887.98112.fe"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867327666201006153202"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/485439a"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm700948z"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295\u2010015\u20101675\u20109"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2016.11.002"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201609079"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/b111145k"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.46.100192.002333"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1074\u20105521(00)00011\u20109"},{"key":"e_1_2_8_15_1","first-page":"357","article-title":"Inhibition by Cyclosporin A of a Ca2+\u2010Dependent Pore in Heart Mitochondria Activated by Inorganic Phosphate and Oxidative Stress","volume":"255","author":"Crompton M.","year":"1988","journal-title":"The Biochemical journal"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr0503097"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2207"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b11861"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c04376"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2005.1"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168243"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864\u2010017\u20103966\u20101"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13213\u2010018\u20101382\u20107"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2017.03.025"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf334"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz310"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1012"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1710"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.665364"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuv008"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1039\/c5np00099h"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1872\u2010034X.2010.00630.x"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1590\/0074\u201002760180506"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2016.05.063"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jes.2021.12.001"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.352770.125"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid2904.221552"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm300605m"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s41061\u2010023\u201000422\u2010z"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/10.3.516"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.16\u2010107"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.12.013"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.05.052"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.2217\/17460913.2.3.323"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13040438"},{"key":"e_1_2_8_46_1","volume-title":"Performance Standards for Antimicrobial Susceptibility Testing","author":"Weinstein M. 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