Original Article

The Journal of Antibiotics (2008) 61, 285–290; doi:10.1038/ja.2008.40

Oxacyclododecindione, a Novel Inhibitor of IL-4 Signaling from Exserohilum rostratum

Gerhard Erkel1, Hanane Belahmer1, Annegret Serwe1, Timm Anke1, Horst Kunz2, Heinz Kolshorn2, Johannes Liermann3 and Till Opatz3

  1. 1Department of Biotechnology, University of Kaiserslautern, Paul-Ehrlich-Str. 23, D-67663 Kaiserslautern, Germany
  2. 2Institute of Organic Chemistry, University of Mainz, Duesbergweg 10-14, D-55128 Mainz
  3. 3Institute of Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, D-20146 Hamburg

Correspondence: G. Erkel, Department of Biotechnology, University of Kaiserslautern, Paul-Ehrlich-Str. 23, D-67663 Kaiserslautern, Germany. E-mail: erkel@ibwf.de

Received 6 March 2008; Accepted 14 April 2008.

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Abstract

In a screening program for new metabolites from fungi inhibiting the IL-4 mediated signal transduction, a novel chlorinated macrocyclic lactone, designated as oxacyclododecindione, was isolated from fermentations of the imperfect fungus Exserohilum rostratum. The structure was determined by a combination of spectroscopic techniques. Oxacyclododecindione inhibits the IL-4 induced expression of the reporter gene secreted alkaline phosphatase (SEAP) in transiently transfected HepG2 cells with IC50 values of 20~25 ng/ml (54~67.5 nM). Studies on the mode of action of the compound revealed that the inhibition of the IL-4 dependent signaling pathway is caused by blocking the binding of the activated STAT6 transcription factors to the DNA binding site without inhibiting tyrosine phosphorylation. The compound has no antibacterial or antifungal activity.

Keywords:

exserohilum, interleukin-4 signaling, inhibitor, new metabolite

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