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We report\n                      <jats:italic>Streptomyces netropsis<\/jats:italic>\n                      AK308 from Xinjiang's Ailik Lake, which produces mandimycin, a polyene macrolide whose unique C\u201035 dideoxysaccharide is reported to enable phospholipid targeting, thereby potentially circumventing ergosterol\u2010based resistance mechanisms. We evaluated its efficacy against 12 key pathogens and mapped its biosynthetic gene cluster to enable future development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The mandimycin mixture consisting of four congeners (A\u2013D), showed broad\u2010spectrum activity against 12 phytopathogens with EC\u2085\u2080 values ranging from 0.02 to 8.98\u2009\u03bcg\u2009mL\n                      <jats:sup>\u22121<\/jats:sup>\n                      . It outperformed natamycin, particularly against\n                      <jats:italic>Botryosphaeria berengeriana and Valsa ceratosperma.<\/jats:italic>\n                      Genomic analysis revealed the\n                      <jats:italic>snt<\/jats:italic>\n                      biosynthetic cluster, confirmed by disrupting core PKS genes (\n                      <jats:italic>sntM<\/jats:italic>\n                      ,\n                      <jats:italic>sntNII<\/jats:italic>\n                      ) resulting in no production. Functional dissection revealed: (i)\n                      <jats:italic>sntO\u2013sntS<\/jats:italic>\n                      govern atratcynose A synthesis\/attachment (\u0394\n                      <jats:italic>sntO<\/jats:italic>\n                      eliminated all congeners), (ii) Deletion of the regulator gene\n                      <jats:italic>sntT<\/jats:italic>\n                      abolished mandimycin production entirely, whereas inactivation of\n                      <jats:italic>sntU<\/jats:italic>\n                      , a gene putatively involved in precursor synthesis, reduced the yield by 44.7%, and (iii) overexpression of individual\n                      <jats:italic>snt<\/jats:italic>\n                      genes (\n                      <jats:italic>A<\/jats:italic>\n                      ,\n                      <jats:italic>B<\/jats:italic>\n                      ,\n                      <jats:italic>T<\/jats:italic>\n                      ,\n                      <jats:italic>U<\/jats:italic>\n                      ) consistently increased the relative abundance of monoglycosylated congeners (B\/D) over fully glycosylated ones (A\/C), directly identifying C\u201035 glycosylation as the major biosynthetic bottleneck.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>\n                      This study identifies mandimycin as a potential agricultural antifungal agent. The validation of the\n                      <jats:italic>snt<\/jats:italic>\n                      cluster reveals the key role of C\u201035 glycosylation in limiting production, offering a pathway for targeted metabolic engineering to enhance yield and improve sustainable crop protection. \u00a9 2026 Society of Chemical Industry.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ps.70717","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T04:35:17Z","timestamp":1773376517000},"page":"6342-6353","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Functional insights into the biosynthesis of antifungal mandimycin"],"prefix":"10.1002","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5238-8356","authenticated-orcid":false,"given":"Xing","family":"Han","sequence":"first","affiliation":[{"name":"Modern Agricultural Science and Technology 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