{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T14:56:13Z","timestamp":1775055373598,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["U22A20582"],"award-info":[{"award-number":["U22A20582"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32100051"],"award-info":[{"award-number":["32100051"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32070054"],"award-info":[{"award-number":["32070054"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["ZR2021ZD28"],"award-info":[{"award-number":["ZR2021ZD28"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"crossref","award":["202172002"],"award-info":[{"award-number":["202172002"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>With the increasing emergence of multidrug-resistant (MDR) bacteria, there is an urgent need to discover new antibiotics. In this study, genome mining coupled with anti-bacterial assay guided the targeted isolation of two new heptapeptides nobilamide Q3 (1) and R3 (2). These compounds were identified as new stereoisomers of the known scaffold A-3302-B (3). The structures of these compounds were elucidated through a combination of MS, NMR spectroscopy and Marfey\u2019s analysis. Anti-MDR bacterial assays showed that compounds 2 and 3 exhibited effective growth inhibition against the Gram-positive MDR bacterial strain Staphylococcus aureus CCARM 3090 with MIC values of 3.25\u20136.5 \u03bcg\/mL. Notably, our study reveals stereochemistry-dependent differences in their antibacterial activities, providing new insights into the structure\u2013activity relationship of this class of peptides. Finally, an analysis of the biosynthetic gene cluster responsible for their production was conducted. This study underscores the significance of exploring cold-seep environments as a reservoir for discovering new antibiotics and provides a structural starting point for the future optimization of antimicrobial peptides.<\/jats:p>","DOI":"10.3390\/molecules31030547","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T12:51:56Z","timestamp":1770209516000},"page":"547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genome-Driven Discovery of Anti-MDR Bacterial Heptapeptides from a Cold-Seep-Derived Bacillus Strain"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9662-3664","authenticated-orcid":false,"given":"Hongcheng","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongmeng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaishuai","family":"Xing","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1598-3217","authenticated-orcid":false,"given":"Wenli","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"},{"name":"State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China"},{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"ref_2","unstructured":"(2024, May 17). 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