biostudies-literatureBorner FNCCIH NIH HHSDeutsche ForschungsgemeinschaftNHLBI NIH HHSNIGMS NIH HHSe2205604https://www.ebi.ac.uk/biostudies/studies/S-EPMC9951388biostudies-literatureUnknown10(6)Specialized pro-resolving mediators (SPM), primarily produced in innate immune cells, exert crucial bioactions for resolving inflammation. Among various lipoxygenases (LOX), 15-LOX-1 is key for SPM biosynthesis, but cellular activation principles of 15-LOX-1 are unexplored. It was shown that 3-O-acetyl-11-keto-β-boswellic acid (AKBA) shifts 5-LOX regiospecificity from 5- to 12-lipoxygenation products. Here, it is demonstrated that AKBA additionally activates cellular 15-LOX-1 via an allosteric site accomplishing robust SPM formation in innate immune cells, particularly in M2 macrophages. Compared to ionophore, AKBA-induced LOX activation is Ca²⁺ - and phosphorylation-independent, with modest induction of 5-LOX products. AKBA docks into a groove between the catalytic and regulatoAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Allosteric Activation of 15-Lipoxygenase-1 by Boswellic Acid Induces the Lipid Mediator Class Switch to Promote Resolution of Inflammation.PMC9951388P50 AT002776NIH HL107887AHA 16GRNT31000010NIH R15GM143724SFB1278/1 Polytarget 316213987SFB 1127/2 ChemBioSys 239748522NIH P50AT002776R15 GM143724R01 HL107887Gilbert NCGerstmeier JGomez MJordan PMNewcomer MEBorner FRossi APace SWerz OfalseAllosteric Activation of 15-Lipoxygenase-1 by Boswellic Acid Induces the Lipid Mediator Class Switch to Promote Resolution of Inflammation.Specialized pro-resolving mediators (SPM), primarily produced in innate immune cells, exert crucial bioactions for resolving inflammation. Among various lipoxygenases (LOX), 15-LOX-1 is key for SPM biosynthesis, but cellular activation principles of 15-LOX-1 are unexplored. It was shown that 3-O-acetyl-11-keto-β-boswellic acid (AKBA) shifts 5-LOX regiospecificity from 5- to 12-lipoxygenation products. Here, it is demonstrated that AKBA additionally activates cellular 15-LOX-1 via an allosteric site accomplishing robust SPM formation in innate immune cells, particularly in M2 macrophages. Compared to ionophore, AKBA-induced LOX activation is Ca²⁺ - and phosphorylation-independent, with modest induction of 5-LOX products. AKBA docks into a groove between the catalytic and regulato2023-01-01T00:00:00Z2023 Feb2026-05-29T05:28:03.832Z2025-02-18T23:44:19.683ZS-EPMC99513883656726810.1002/advs.202205604