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Harnessing Enzymatic Promiscuity in Myxochelin Biosynthesis for the Production of 5‐Lipoxygenase Inhibitors |
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| Authors: | Juliane Korp Stefanie König Dr. Sebastian Schieferdecker Dr. Hans‐Martin Dahse Prof. Dr. Gabriele M. König Prof. Dr. Oliver Werz Dr. Markus Nett |
| Affiliation: | 1. Leibniz Institute for Natural Product Research and Infection Biology, Hans Kn?ll Institute, Jena, Germany;2. Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-Universit?t Jena, Jena, Germany;3. Institute for Pharmaceutical Biology, Rheinische Friedrich-Wilhelms-Universit?t Bonn, Bonn, Germany |
| 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. |
| Keywords: | biosynthesis lipoxygenases myxochelin siderophores substrate tolerance |