More than 50 years ago,Barton and Cohen correlated the structures of many phenol-coupled natural products of higher plants to the radical mechanism of oxidative phenol coupling.In 1997 Lewis et al.reported that in some plant families the lignan formation via oxidative phenol coupling is a two-enzyme-process.The late Meinhart Zenk showed that P450 enzymes catalyze regio-and stereoselective-intramolecular-oxidative phenol coupling in the biosynthesis of several alkaloids in plants and mammals.Our aim is directed toward characterizing the enzymes that are responsible for the regio-and stereoselective oxidative phenol coupling in fungi.For that reason we have chosen the filamentous fungus Aspergillus niger,producers of the dimeric metabolites kotanin,as a model system.In order to develop an assay system we synthesized the dimeric target molecules as well as the monomeric precursor demethylsiderin specifically 13C-labeled.Feeding studies revealed the polyketide origin and the regio-and atropselective dehydrodimerization of demethylsiderin.Progress towards the identification of the biosynthetic gene cluster and enzymes involved in these transformations as well as in vivo studies and characterization of the P450 enzymes will be discussed.