Nature Communications (Dec 2017)

Warhead biosynthesis and the origin of structural diversity in hydroxamate metalloproteinase inhibitors

  • Franziska Leipoldt,
  • Javier Santos-Aberturas,
  • Dennis P. Stegmann,
  • Felix Wolf,
  • Andreas Kulik,
  • Rodney Lacret,
  • Désirée Popadić,
  • Daniela Keinhörster,
  • Norbert Kirchner,
  • Paulina Bekiesch,
  • Harald Gross,
  • Andrew W. Truman,
  • Leonard Kaysser

DOI
https://doi.org/10.1038/s41467-017-01975-6
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 12

Abstract

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Metalloproteinase inhibitors are leads for drug development, but their biosynthetic pathways are often unknown. Here the authors show that the acyl branched warhead of actinonin and matlystatins derives from an ethylmalonyl-CoA-like pathway and the structural diversity of matlystatins is due to the activity of a decarboxylase-dehydrogenase enzyme.