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This study explored the bioactive potential of metabolites from the marine actinomycete\n                      <jats:italic>Streptomyces zaomyceticus<\/jats:italic>\n                      , isolated from a deep-sea sediment sample off Sharm El-Sheikh, Egypt. Bioactivity-guided fractionation led to the isolation and structural elucidation of SPIROST-8-EN-11-ONE, 3-HYDROXY- (SEOH), identified as a novel spirostenoid. SEOH exhibited significant broad-spectrum in vitro growth inhibition against a diverse panel of aquaculture-relevant pathogens, including Gram-positive and Gram-negative bacteria, and opportunistic fungi. It demonstrated potent minimum inhibitory concentrations (MICs) ranging from 0.25 to 1.0 \u00b5g\/mL, notably effective against multidrug-resistant (MDR)\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      (0.25 \u00b5g\/mL) and\n                      <jats:italic>Enterococcus faecalis<\/jats:italic>\n                      (0.5 \u00b5g\/mL). Scanning electron microscopy (SEM) revealed that SEOH treatment (2\u00d7\u2009MIC) induced significant morphological alterations, including visible cell surface modifications and reduced cell numbers, in both bacterial (\n                      <jats:italic>E. faecalis<\/jats:italic>\n                      ,\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      ,\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      ) and fungal (\n                      <jats:italic>C. albicans<\/jats:italic>\n                      ) pathogens. Preliminary cytotoxicity assessment using the MTT assay on HepG2 cells yielded a promising IC\u2085\u2080 value of 71.76\u2009\u00b1\u20090.62 \u00b5g\/ml, indicating a favorable in vitro safety profile. The novel structure of SEOH coupled with its potent, broad-spectrum in vitro antimicrobial activity against crucial aquaculture pathogens positions it as a highly promising candidate. These compelling in vitro findings strongly warrant comprehensive in vivo efficacy and safety studies to fully establish SEOH\u2019s potential as a novel therapeutic agent or feed additive for advancing aquaculture sustainability and animal health.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      \u2022\n                      <jats:italic>Novel Spirostenoid Discovery: SEOH, a new spirostenoid from Streptomyces zaomyceticus, was identified<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      \u2022\n                      <jats:italic>Potent Broad-Spectrum Activity: It shows strong inhibition against MDR aquaculture pathogens (MICs = 1.0 \u00b5g\/mL)<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      \u2022\n                      <jats:italic>Warrants Further Study: Its promising safety profile and potency merit in vivo testing for aquaculture use<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00253-025-13664-2","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T20:44:03Z","timestamp":1766177043000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SEOH, a novel marine-derived spirostenoid: potent broad-spectrum antimicrobial activity against multidrug-resistant aquaculture pathogens"],"prefix":"10.1007","volume":"109","author":[{"given":"Rewan","family":"Abdelaziz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamal","family":"EL-Didamony","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0825-9776","authenticated-orcid":false,"given":"Azza S.","family":"El-Demerdash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania A.","family":"ElDaly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"13664_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsi.2024.109496","author":"R Abdelaziz","year":"2024","unstructured":"Abdelaziz R, Elsheshtawy HM, El-Houseiny W, Aloufi AS, Alwutayd KM, Mansour AT, Hadad G, Arisha AH, El-Murr AE, M. 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