{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:21:06Z","timestamp":1791591666245,"version":"4.3.4"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2014,1,31]],"date-time":"2014-01-31T00:00:00Z","timestamp":1391126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Concerning the requirements of effective drug candidates to combat against high rising multidrug resistant pathogens, we isolated three new linear lipopeptides, gageostatins A\u2013C (1\u20133), consisting of hepta-peptides and new 3-\u03b2-hydroxy fatty acids from the fermentation broth of a marine-derived bacterium Bacillus subtilis. Their structures were elucidated by analyzing a combination of extensive 1D, 2D NMR spectroscopic data and high resolution ESIMS data. Fatty acids, namely 3-\u03b2-hydroxy-11-methyltridecanoic and  3-\u03b2-hydroxy-9,11-dimethyltridecanoic acids were characterized in lipopeptides 1 and 2, respectively, whereas an unsaturated fatty acid (E)-7,9-dimethylundec-2-enoic acid was assigned in 3. The 3R configuration of the stereocenter of 3-\u03b2-hydroxy fatty acids in 1 and 2 was established by Mosher\u2019s MTPA method. The absolute stereochemistry of amino acid residues in 1\u20133 was ascertained by acid hydrolysis followed by Marfey\u2019s derivatization studies. Gageostatins 1\u20133 exhibited good antifungal activities with MICs values of  4\u201332 \u00b5g\/mL when tested against pathogenic fungi (R. solani, B. cinerea and C. acutatum) and moderate antibacterial activity against bacteria (B. subtilis, S. aeureus, S. typhi and  P. aeruginosa) with MICs values of 8\u201364 \u00b5g\/mL. Futhermore, gageostatins 1\u20133 displayed cytotoxicity against six human cancer cell lines with GI50 values of 4.6\u201319.6 \u00b5g\/mL. It is also noteworthy that mixed compounds 1+2 displayed better antifungal and cytotoxic activities than individuals.<\/jats:p>","DOI":"10.3390\/md12020871","type":"journal-article","created":{"date-parts":[[2014,1,31]],"date-time":"2014-01-31T11:12:32Z","timestamp":1391166752000},"page":"871-885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Gageostatins A\u2013C, Antimicrobial Linear Lipopeptides from a Marine Bacillus subtilis"],"prefix":"10.3390","volume":"12","author":[{"given":"Fakir","family":"Tareq","sequence":"first","affiliation":[{"name":"Department of Marine Biotechnology, University of Science and Technology, 176 Gajung-dong, 217 Gajungro Yuseong-gu, Daejeon, 305-350, Korea"},{"name":"Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, Ansan, 426-744, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Lee","sequence":"additional","affiliation":[{"name":"Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, Ansan, 426-744, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyi-Seung","family":"Lee","sequence":"additional","affiliation":[{"name":"Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, Ansan, 426-744, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, Ansan, 426-744, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4814-943X","authenticated-orcid":false,"given":"Yeon-Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, Ansan, 426-744, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Marine Biotechnology, University of Science and Technology, 176 Gajung-dong, 217 Gajungro Yuseong-gu, Daejeon, 305-350, Korea"},{"name":"Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, Ansan, 426-744, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3390\/md8020313","article-title":"Review: Bioactive sesterterpenes and triterpenes from marine sponges: Occurrence and pharmacological significance","volume":"8","author":"Ebada","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/anie.200390115","article-title":"Salinosporamide A: A highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus salinospora","volume":"42","author":"Feling","year":"2003","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.3390\/su2061602","article-title":"Review: Resistance of microorganisms to extreme environmental conditions and its contribution to astrobiology","volume":"2","author":"Rampelotto","year":"2010","journal-title":"Sustainability"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.tim.2008.03.004","article-title":"Ecology and genomics of Bacillus subtilis","volume":"16","author":"Earl","year":"2008","journal-title":"Trends Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/nbt1325","article-title":"Comparative analysis of the complete genome sequence of the plant growth-promoting bacterium Bacillus amyloliquefaciens FZB42","volume":"25","author":"Chen","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/36786","article-title":"The complete genome sequence of the gram-positive bacterium Bacillus subtilis","volume":"390","author":"Kunst","year":"1997","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1128\/JB.01351-10","article-title":"Genome sequence of Bacillus subtilis subsp. spizizenii gtP20b, isolated from the Indian ocean","volume":"193","author":"Fan","year":"2011","journal-title":"J. Bacteriol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1021\/np100853e","article-title":"Non-peptide metabolites from the genus Bacillus","volume":"74","author":"Hamdache","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_9","unstructured":"Vilas, A.M. (2011). Science against Microbial Pathogens: Communicating Current Research and Technological Advances, Formatex."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.3390\/md11082846","article-title":"Diversity of secondary metabolites from marine Bacillus species: Chemistry and biological activity","volume":"11","author":"Mondol","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1021\/bm9011453","article-title":"Interaction between the natural lipopeptide [Glu1, Asp5] Surfactin-C15 and hemoglobin in aqueous solution","volume":"11","author":"Zou","year":"2010","journal-title":"Biomacromolecules"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1111\/j.1365-2958.2005.04587.x","article-title":"Bacillus subtilis antibiotics: Structures, syntheses and specific functions","volume":"5","author":"Stein","year":"2005","journal-title":"Mol. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10630","DOI":"10.1021\/bi8011675","article-title":"Antimicrobial lipopolypeptides composed of palmitoyl di- and tricationic peptides: In vitro and in vivo activities, self-assembly to nanostructures, and a plausible mode of action","volume":"47","author":"Makovitzki","year":"2008","journal-title":"Biochemistry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"479","DOI":"10.2174\/138920306779025620","article-title":"Host defense peptides and lipopeptides: Modes of action and potential candidates for the treatment of bacterial and fungal infections","volume":"7","author":"Shai","year":"2006","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.bbamem.2006.02.009","article-title":"Mode of action of the new antibiotic for Gram-positive pathogens daptomycin: Comparison with cationic antimicrobial peptides and lipopeptides","volume":"1758","author":"Straus","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5451","DOI":"10.1128\/AEM.65.12.5451-5458.1999","article-title":"Permeabilization of fungal membranes by plant defensins inhibits fungal growth","volume":"65","author":"Thevissen","year":"1999","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1099\/13500872-141-8-1875","article-title":"Hydrophobic properties of the cell surface of Candida albicans: A role in aggregation","volume":"14","author":"Hobden","year":"1995","journal-title":"Microbiology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1080\/02681219780000961","article-title":"Lipopeptide inhibitors of fungal glucan synthase","volume":"35","author":"Kurtz","year":"1997","journal-title":"J. Med. Vet. Mycol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1126\/science.1063391","article-title":"Antarctic sea ice\u2014A habitat for extremophiles","volume":"295","author":"Thomas","year":"2002","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/ja.2010.56","article-title":"Bioprospecting microbial natural product libraries from the marine environment for drug discovery","volume":"63","author":"Liu","year":"2010","journal-title":"J. Antibiot."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/BF02908688","article-title":"Determination of d-amino acids. II. Use of a bifunctional reagent, 1-5-difluoro-2,4-dinitrobenzene","volume":"49","author":"Marfey","year":"1984","journal-title":"Carlsberg Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4092","DOI":"10.1021\/ja00011a006","article-title":"High-field FT NMR application of Mosher\u2019s method. The absolute configuration of marine terpenoids","volume":"113","author":"Ohtani","year":"1991","journal-title":"J. Am. Chem. Soc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3778","DOI":"10.1021\/jo048643a","article-title":"Determining the absolute stereochemistry of secondary\/secondary diols by 1H NMR: Basis and applications","volume":"70","author":"Freire","year":"2005","journal-title":"J. Org. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11578","DOI":"10.1021\/jf802772a","article-title":"Enantioselective analysis of 2- and 3-hydroxy fatty acids in food samples","volume":"56","author":"Jenske","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s10989-005-6790-4","article-title":"Solid-phase synthesis of surfactin, a powerful biosurfactant produced by Bacillus subtilis, and of four analogues","volume":"11","author":"Maider","year":"2005","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1021\/np8002673","article-title":"Antibacterial cannabinoids from Cannabis sativa: A structure-activity study","volume":"71","author":"Appendio","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1016\/j.phytochem.2004.10.009","article-title":"Antibacterial and resistance modifying activity of Rosmarinus officinalis","volume":"65","author":"Oluwatuyi","year":"2004","journal-title":"Phytochemistry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.phytochem.2004.02.005","article-title":"Chemical composition and antimicrobial activity of the essential oil of Scutellaria barbata","volume":"65","author":"Yu","year":"2004","journal-title":"Phytochemistry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1093\/jnci\/82.13.1107","article-title":"New colorimetric cytotoxicity assay for anticancer-drug screening","volume":"82","author":"Skehan","year":"1990","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_30","first-page":"119","article-title":"Surfactin\u2014A review on biosynthesis, fermentation, purification and applications","volume":"48","author":"Shaligram","year":"2010","journal-title":"Food Technol. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.bbalip.2003.09.004","article-title":"A novel lipopeptide, an inhibitor of bacterial adhesion, from the thermophilic and halotolerant subsurface Bacillus licheniformis strain 603","volume":"1634","author":"Batrakov","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1007\/s11274-010-0412-9","article-title":"Characterization of lipopeptides from Paenibacillus sp. (IIRAC30) suppressing Rhizoctonia solani","volume":"26","author":"Canova","year":"2010","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.febslet.2007.01.059","article-title":"Surfactin from Bacillus subtilis displays anti-proliferative effect via apoptosis induction, cell cycle arrest and survival signaling suppression","volume":"581","author":"Kim","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/j.peptides.2007.06.014","article-title":"Induction of apoptosis in human leukemia K562 cells by cyclic lipopeptide from Bacillus subtilis natto T-2","volume":"28","author":"Wang","year":"2007","journal-title":"Peptides"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1021\/np100408y","article-title":"Antifungal lipopeptides from Bacillus amyloliquefaciens strain BO7","volume":"74","author":"Romano","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0922-338X(97)82784-5","article-title":"Production and properties of a lipopeptide biosurfactant from Bacillus subtilis C9","volume":"84","author":"Kim","year":"1997","journal-title":"J. Ferment. Bioeng."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1111\/j.1365-2672.2004.02356.x","article-title":"Purification and characterization of a lipopeptide produced by Bacillus thuringiensis CMB26","volume":"97","author":"Kim","year":"2004","journal-title":"J. Appl. Microbiol."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/12\/2\/871\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:07:55Z","timestamp":1760216875000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/12\/2\/871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,31]]},"references-count":37,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2014,2]]}},"alternative-id":["md12020871"],"URL":"https:\/\/doi.org\/10.3390\/md12020871","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,31]]}}}