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The widespread use of antifungal agents has led to the increasing emergence of drug resistance, underscoring the urgent need for novel antifungal strategies.\n                      <jats:italic toggle=\"yes\">Bacillus altitudinis<\/jats:italic>\n                      AS19 has been found to produce a substance with specific antimicrobial activity against\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      under iron-deficient conditions. In this study, the fermentation medium and culture conditions for siderophore production by AS19 were optimized using response surface methodology (RSM) and an artificial neural network-genetic algorithm (ANN-GA) model. The ANN-GA model demonstrated superior optimization performance compared with RSM. The optimal conditions were pH 6.363, sucrose 29.730 g\/L, and KH\n                      <jats:sub>2<\/jats:sub>\n                      PO\n                      <jats:sub>4<\/jats:sub>\n                      0.185 g\/L, under which the yield increased more than twofold compared with the pre-optimization level of 26.53%. To further investigate the antimicrobial mechanism, molecular docking and dynamics simulations were employed to virtually screen siderophores with anti-\n                      <jats:italic toggle=\"yes\">C<\/jats:italic>\n                      .\n                      <jats:italic toggle=\"yes\">albicans<\/jats:italic>\n                      activity and identify their potential targets. Among the candidates, Nocardamin Glucuronide was prioritized as the top hit, and the presence of desferrioxamine-type siderophores produced by AS19 was subsequently confirmed by LC-MS, validating the\n                      <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                      predictions. In addition,\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      assays were performed to determine the minimum inhibitory concentration, minimum fungicidal concentration, and time-kill kinetics of the crude siderophore extract. The time-kill curve clearly demonstrated its potent antimicrobial activity against\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      . Overall, this study provides both a theoretical basis and experimental evidence for the development of novel siderophore-based antimicrobial agents targeting\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                        is a common opportunistic fungal pathogen responsible for severe infections in immunocompromised individuals, while increasing antifungal resistance has reduced the effectiveness of current treatments. In this study, a natural compound with specific anti-\n                        <jats:italic toggle=\"yes\">C<\/jats:italic>\n                        .\n                        <jats:italic toggle=\"yes\">albicans<\/jats:italic>\n                        activity produced by\n                        <jats:italic toggle=\"yes\">Bacillus altitudinis<\/jats:italic>\n                        AS19 under iron-deficient conditions was investigated. Artificial intelligence-based models were used to optimize fermentation conditions, significantly improving production efficiency. Molecular simulations were performed to explore the potential antimicrobial mechanism, and\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        assays confirmed its antifungal activity. These results provide a basis for developing novel antifungal agents targeting\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        .\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/aem.00815-26","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:12:56Z","timestamp":1785849176000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Data-driven optimization of siderophore fermentation by\n                    <i>Bacillus altitudinis<\/i>\n                    AS19 and investigation of AS19\u2019s antifungal properties against\n                    <i>Candida albicans<\/i>"],"prefix":"10.1128","volume":"92","author":[{"given":"Chenjian","family":"Li","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035y7a716","id-type":"ROR","asserted-by":"publisher"}],"name":"Engineering Research Center of Medical Biotechnology, School of Biology and Engineering, Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zexin","family":"Gao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035y7a716","id-type":"ROR","asserted-by":"publisher"}],"name":"Engineering Research Center of Medical Biotechnology, School of Biology and Engineering, Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghai","family":"Ke","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035y7a716","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Basic Medicine Science, Guizhou 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