{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:15:25Z","timestamp":1793153725751,"version":"4.5.0"},"reference-count":14,"publisher":"American Chemical Society (ACS)","issue":"43","license":[{"start":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T00:00:00Z","timestamp":1571184000000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AT009874"],"award-info":[{"award-number":["R01 AT009874"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AI109673"],"award-info":[{"award-number":["U19 AI109673"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Bacterial symbionts frequently provide chemical defenses for their hosts, and such systems can provide discovery pathways to new antifungals and structurally intriguing metabolites. This report describes a small family of naturally occurring small molecules with chimeric structures and a mixed biosynthesis that features an unexpected but key nonenzymatic step. An insect-associated Pseudomonas protegens strain\u2019s activity in an in vivo murine candidiasis assay led to the discovery of a family of highly hydrogen-deficient metabolites. Bioactivity- and mass-guided fractionation led to the pyonitrins, highly complex aromatic metabolites in which 10 of the 20 carbons are quaternary, and 7 of them are contiguous. The P. protegens genome revealed that the production of the pyonitrins is the result of a spontaneous reaction between biosynthetic intermediates of two well-studied Pseudomonas metabolites, pyochelin and pyrrolnitrin. The combined discovery of the pyonitrins and identification of the responsible biosynthetic gene clusters revealed an unexpected biosynthetic route that would have prevented the discovery of these metabolites by bioinformatic analysis alone.<\/jats:p>","DOI":"10.1021\/jacs.9b09739","type":"journal-article","created":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T17:53:30Z","timestamp":1570730010000},"page":"17098-17101","source":"Crossref","is-referenced-by-count":44,"title":["Pyonitrins\nA\u2013D: Chimeric Natural Products Produced\nby\n                    <i>Pseudomonas protegens<\/i>"],"prefix":"10.1021","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7986-5610","authenticated-orcid":true,"given":"Emily","family":"Mevers","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School , 240 Longwood Avenue , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Sauri\u0301","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. , , 33 Avenue Louis Pasteur , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J. N.","family":"Helfrich","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School , 240 Longwood Avenue , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Henke","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School , 240 Longwood Avenue , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"Barns","sequence":"additional","affiliation":[{"name":"University of Wisconsin\u2500Madison , , , ,","place":["Madison, Wisconsin, United States, 53705"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim S.","family":"Bugni","sequence":"additional","affiliation":[{"name":"University of Wisconsin\u2500Madison , , , ,","place":["Madison, Wisconsin, United States, 53705"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Andes","sequence":"additional","affiliation":[{"name":"University of Wisconsin School of Medicine and Public Health , , , ,","place":["Madison, Wisconsin, United States, 53705"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron R.","family":"Currie","sequence":"additional","affiliation":[{"name":"University of Wisconsin\u2500Madison , , , ,","place":["Madison, Wisconsin, United States, 53705"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0213-8356","authenticated-orcid":true,"given":"Jon","family":"Clardy","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School , 240 Longwood Avenue , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2019,10,10]]},"reference":[{"issue":"38","key":"2026090108251974900_cit1","doi-asserted-by":"publisher","first-page":"12324","DOI":"10.1021\/jacs.6b07588","article-title":"Homodimericin\nA: A Complex Hexacyclic Fungal Metabolite","volume":"138","author":"Mevers","year":"2016","journal-title":"J.\nAm. 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Microbiol."},{"issue":"6782","key":"2026090108251974900_cit5","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/35011098","article-title":"A role for Excreted\nQuinones in Extracellular Electron\nTransfer","volume":"405","author":"Newman","year":"2000","journal-title":"Nature"},{"issue":"1","key":"2026090108251974900_cit6","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1128\/jb.100.1.310-318.1969","article-title":"Mechanism of Action\nof the Antifungal Antibiotic Pyrrolnitrin","volume":"100","author":"Tripathi","year":"1969","journal-title":"J.\nBacteriol."},{"issue":"11","key":"2026090108251974900_cit7","doi-asserted-by":"publisher","first-page":"5364","DOI":"10.1128\/jb.170.11.5364-5367.1988","article-title":"Isolation and Characterization of Pseudomonas aeruginosa Mutants Requiring Salicylic Acid for Pyochelin\nBiosynthesis","volume":"170","author":"Ankenbauer","year":"1988","journal-title":"J. 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Biol."},{"issue":"38","key":"2026090108251974900_cit14","doi-asserted-by":"publisher","first-page":"9980","DOI":"10.1002\/anie.201303449","article-title":"Discovery of McbB, an Enzyme Catalyzing the \u03b2-carboline Skeleton\nConstruction in the Marinacarboline Biosyntethic Pathway","volume":"52","author":"Chen","year":"2013","journal-title":"Angew. Chem., Int. 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