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Among various lipoxygenases (LOX), 15\u2010LOX\u20101\u00a0is key for SPM biosynthesis, but cellular activation principles of 15\u2010LOX\u20101\u00a0are unexplored. It was shown that 3\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010acetyl\u201011\u2010keto\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010boswellic acid (AKBA) shifts 5\u2010LOX regiospecificity from 5\u2010 to 12\u2010lipoxygenation products. Here, it is demonstrated that AKBA additionally activates cellular 15\u2010LOX\u20101\u00a0via an allosteric site accomplishing robust SPM formation in innate immune cells, particularly in M2\u00a0macrophages. Compared to ionophore, AKBA\u2010induced LOX activation is Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010 and phosphorylation\u2010independent, with modest induction of 5\u2010LOX products. AKBA docks into a groove between the catalytic and regulatory domains of 15\u2010LOX\u20101\u00a0interacting with R98; replacement of R98\u00a0by alanine abolishes AKBA\u2010induced 15\u2010LOX product formation in HEK293\u00a0cells. In zymosan\u2010induced murine peritonitis, AKBA strikingly elevates SPM levels and promotes inflammation resolution. Together, targeted allosteric modulation of LOX activities governs SPM formation and offers new concepts for inflammation resolution pharmacotherapy.\n                  <\/jats:p>","DOI":"10.1002\/advs.202205604","type":"journal-article","created":{"date-parts":[[2022,12,25]],"date-time":"2022-12-25T22:52:45Z","timestamp":1672008765000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Allosteric Activation of 15\u2010Lipoxygenase\u20101 by Boswellic Acid Induces the Lipid Mediator Class Switch to Promote Resolution of Inflammation"],"prefix":"10.1002","volume":"10","author":[{"given":"Friedemann","family":"B\u00f6rner","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical\/Medicinal Chemistry Institute of Pharmacy Friedrich\u2010Schiller\u2010University Jena  Philosophenweg 14 07743 Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Pace","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical\/Medicinal Chemistry Institute of Pharmacy Friedrich\u2010Schiller\u2010University Jena  Philosophenweg 14 07743 Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Jordan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical\/Medicinal Chemistry Institute of Pharmacy Friedrich\u2010Schiller\u2010University Jena  Philosophenweg 14 07743 Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Gerstmeier","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical\/Medicinal Chemistry Institute of Pharmacy Friedrich\u2010Schiller\u2010University Jena  Philosophenweg 14 07743 Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Gomez","sequence":"additional","affiliation":[{"name":"Evonik Operations GmbH  Kirschenallee 45 64293 Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy School of Medicine and Surgery University of Naples Federico II  Via D. 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