Stereoselective oxidative phenol coupling in filamentous fungi

MICHAEL MÜLLER
Institut für Pharmazeutische Wissenschaften
Universität Freiburg
Albertstr. 25
D-79104 Freiburg
michael.mueller@pharmazie.uni-freiburg.de
http://www.pharmazie.uni-freiburg.de/chemie/

The oxidative phenol coupling can be observed in diverse organisms, especially plants and fungi. Even in closely related species often different regio- and stereoselectivities are observed at this reaction step. Hence biaryl biosynthesis is an excellent example for the evolution of metabolic diversity and shall be studied under this aspect. Besides, the stereoselective oxidative phenol coupling is also interesting from the chemical point of view, because the chemical alternatives are usually very demanding.

We are interested in the selective dimerization of coumarins in filamentous fungi of the genus Aspergillus. Here we focus on A. niger producing kotanin. Additionally, we are studying the phenolic coupling of Semi-Vioxanthin and its derivatives to Vioxanthin in Penicillium citreo-viride. A chemical access to the monomeric and dimeric natural products was developed and analytical assays could be established easily. Feeding experiments with ¹³C-labelled monomers revealed clearly that a regio- and stereoselective oxidative phenol coupling step is indeed part of kotanin and vioxanthin biosynthesis, respectively.

To identify the enzymatic activity of the oxidative phenol coupling a cosmid library of A. niger was generated. The cosmids can be transformed in suitable Aspergillus host strains and then be screened for enzymatic activity.

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