ChemBioChem 2015-11-01

Harnessing Enzymatic Promiscuity in Myxochelin Biosynthesis for the Production of 5-Lipoxygenase Inhibitors.

Juliane Korp, Stefanie König, Sebastian Schieferdecker, Hans-Martin Dahse, Gabriele M König, Oliver Werz, Markus Nett

Index: ChemBioChem. 16(17) , 2445-50, (2015)

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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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.