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The corresponding biosynthetic gene cluster required for their production, however, has not been experimentally assigned. Based on targeted genetics, metabolite profiling, and structure analysis, we identify a divergent syringomycin-type nonribosomal peptide synthetase gene cluster in P. syringae DSM 1242 and show that psyt is the syringotoxin biosynthetic gene cluster. Deletion of psyt abolishes syringotoxin production and renders the mutant susceptible to grazing by the amoebal predator Dictyostelium discoideum. Besides nanomolar amoebicidal activity, syringotoxin B shows strong antifungal activity, particularly against Candida pathogens. Comparative genomic and structural analyses place psyt within the syringomycin-type lipopeptide family, while the activity loss after macrolactone opening links syringotoxin bioactivity to its cyclic lipopeptide architecture. Together, this work assigns the biosynthetic origin of syringotoxin and establishes this cyclic lipopeptide as a defense factor required for full resistance of P. syringae to amoebal predation.<\/jats:p>","DOI":"10.1021\/acschembio.6c00589","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:01:38Z","timestamp":1790946098000},"page":"2734-2742","source":"Crossref","is-referenced-by-count":0,"title":["Syringotoxin Biosynthetic Gene Cluster Required for Antiamoebal Defense in\n                    <i>Pseudomonas syringae<\/i>"],"prefix":"10.1021","volume":"21","author":[{"given":"Ying","family":"Huang","sequence":"first","affiliation":[{"name":"Leibniz Institute for Natural Product Research and Infection Biology, Hans Kn\u00f6ll Institute , , Beutenbergstra\u00dfe 11a , ,","place":["Jena, Germany, 07745"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaibing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Natural Product Research and Infection Biology, Hans Kn\u00f6ll Institute , , Beutenbergstra\u00dfe 11a , ,","place":["Jena, Germany, 07745"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Reimer","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Natural Product Research and Infection Biology, Hans Kn\u00f6ll Institute , , Beutenbergstra\u00dfe 11a , ,","place":["Jena, Germany, 07745"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grit","family":"Walther","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Natural Product Research and Infection Biology, Hans Kn\u00f6ll Institute , , Beutenbergstra\u00dfe 11a , ,","place":["Jena, Germany, 07745"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Willing","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Natural Product Research and Infection Biology, Hans Kn\u00f6ll Institute , , Beutenbergstra\u00dfe 11a , ,","place":["Jena, Germany, 07745"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7260-9921","authenticated-orcid":true,"given":"Pierre","family":"Stallforth","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Natural Product Research and Infection Biology, Hans Kn\u00f6ll Institute , , Beutenbergstra\u00dfe 11a , ,","place":["Jena, Germany, 07745"]},{"name":"Friedrich Schiller University Jena , , Humboldtstra\u00dfe 10 , ,","place":["Jena, Germany, 07743"]},{"name":"Friedrich Schiller University Jena , , F\u00fcrstengraben 1 , ,","place":["Jena, Germany, 07743"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"issue":"7","key":"2026101523064399200_cit1","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1039\/c5np00013k","article-title":"Natural products in soil microbe interactions and evolution","volume":"32","author":"Traxler","year":"2015","journal-title":"Nat. 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