title: Harnessing Enzymatic Promiscuity in Myxochelin Biosynthesis for the Production of 5-Lipoxygenase Inhibitors.
abstract: The siderophore myxochelin A is a potent inhibitor of human 5-lipoxygenase (5-LO). To clarify whether the iron-chelating properties of myxochelin A are responsible for this activity, several analogues of this compound were generated in the native producer Pyxidicoccus fallax by precursor-directed biosynthesis. Testing in a cell-free assay unveiled three derivatives with bioactivity comparable with that of myxochelin A. Furthermore, it became evident that inhibition of 5-LO by myxochelins does not correlate with their iron affinities.
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Adolf-Reichwein-Strasse 23, 07745, Jena, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Korp
authors.affiliation: Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-Universität Jena, Philosophenweg 14, 07743, Jena, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: König
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Adolf-Reichwein-Strasse 23, 07745, Jena, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schieferdecker
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Adolf-Reichwein-Strasse 23, 07745, Jena, Germany.
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Dahse
authors.affiliation: Institute for Pharmaceutical Biology, Rheinische Friedrich-Wilhelms-Universität Bonn, Nussallee 6, 53115, Bonn, Germany.
authors.forename: Gabriele M
authors.initials: GM
authors.lastname: König
authors.affiliation: Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-Universität Jena, Philosophenweg 14, 07743, Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Adolf-Reichwein-Strasse 23, 07745, Jena, Germany. markus.nett@hki-jena.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Nett
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry; D009231:Myxococcales / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D016859:Lipoxygenase Inhibitors; C058735:myxochelin A; D001094:Arachidonate 5-Lipoxygenase; D008239:Lysine
keywords: biosynthesis; lipoxygenases; myxochelin; siderophores; substrate tolerance