{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:27:42Z","timestamp":1788481662835,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"45","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The emergence of multidrug\u2010resistant pathogens presents a major clinical challenge worldwide. The underexplored bacterial genus\n                    <jats:italic>Aquimarina<\/jats:italic>\n                    harbors a large biosynthetic potential for the discovery of new classes of antibiotics with distinctive modes of action, which can be unearthed in a scalable manner using a synthetic bioinformatic natural product approach. Here, the discovery of a pair of linear or cyclic bifunctional cationic lipopeptide antibiotics, aquicidine L and aquicidine C4, with opposite antibacterial spectra, is reported, which are chemically synthesized on the basis of distinct structure prediction of the aquicidine gene cluster from\n                    <jats:italic>Aquimarina<\/jats:italic>\n                    . Aquicidine L mainly targets both anionic lipopolysaccharide and phosphatidylethanolamine in the bacterial membrane and is efficacious against two different meropenem\u2010resistant Gram\u2010negative pathogens in murine peritonitis\u2010sepsis models. In contrast, aquicidine C4 mainly binds to both anionic cardiolipin and phosphatidylglycerol in the membrane and proves effective at treating methicillin\u2010 or vancomycin\u2010resistant Gram\u2010positive pathogen infections in vivo. Owing to the dual\u2010mechanism features of aquicidine L or aquicidine C4, both of them are absent in detectable resistance in laboratory tests. These findings provide a pair of naturally inspired and mechanistically interesting therapeutic leads for evading antimicrobial resistance.\n                  <\/jats:p>","DOI":"10.1002\/advs.202509796","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T03:37:11Z","timestamp":1757648231000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of a Pair of Linear or Cyclic Naturally Inspired Bifunctional Lipopeptide Antibiotics That Overcome Antimicrobial Resistance"],"prefix":"10.1002","volume":"12","author":[{"given":"Lei","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology Shanghai Jiao Tong University  800 Dongchuan Rd. Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology Shanghai Jiao Tong University  800 Dongchuan Rd. Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhu","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology Shanghai Jiao Tong University  800 Dongchuan Rd. 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