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

Chembiochem. 2015 Nov;16(17):2445-50. doi: 10.1002/cbic.201500446. Epub 2015 Oct 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonate 5-Lipoxygenase / chemistry
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Humans
  • Inhibitory Concentration 50
  • Lipoxygenase Inhibitors / chemistry
  • Lipoxygenase Inhibitors / metabolism*
  • Lysine / analogs & derivatives*
  • Lysine / biosynthesis
  • Lysine / chemistry
  • Myxococcales / metabolism
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Lipoxygenase Inhibitors
  • myxochelin A
  • Arachidonate 5-Lipoxygenase
  • Lysine