Harnessing Enzymatic Promiscuity in Myxochelin Biosynthesis for the Production of 5‐Lipoxygenase Inhibitors. Issue 17 (13th October 2015)

• Record Type: Journal Article
• Authors: Korp, Juliane; König, Stefanie; Schieferdecker, Sebastian; Dahse, Hans‐Martin; König, Gabriele M.; Werz, Oliver; Nett, Markus
• Is Part Of: Chembiochem. Volume 16:Issue 17(2015)
• Page Start: 2445
• Page End: 2450
• Publication Date: 2015-10-13
• Subjects: biosynthesis -- lipoxygenases -- myxochelin -- siderophores -- substrate tolerance; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201500446
• Languages: English
• ISSNs: 1439-4227

Abstract

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. Abstract : A series of new myxochelin analogues was generated by precursor‐directed biosynthesis. Some derivatives possess only weak iron‐chelating properties, but are still potent inhibitors of human 5‐lipoxygenase, an enzyme featuring a non‐heme iron atom in its catalytically active site.