Regio- and Stereoselective Oxidative phenol coupling in Aspergillus spp

KATHARINA G HUGENTOBLER; LAURA S. MAZZAFERRO; WOLFGANG HÜTTEL; MICHAEL MÜLLER

Congreso; Biotrans 2015; 2015

Regio- and stereoselective intermolecular oxidative phenol coupling is difficult to achieve by means of classic chemistry. In nature, cytochrome P450-enzyme mediated routes are employed to achieve stereo- and regiocontrol in the synthesis of atropisomeric biarylic compounds[1]. We previously reported the biosynthesis of bicoumarin derivatives by species of the Aspergillus genus[2,3]. KtnC and DesC, two orthologous cytochrome P450 enzymes were proven to each yield one homocoupled product exclusively. While KtnC from Aspergillus niger yields only the 8-8'-P coupled product, DesC from Emericella desertorum gives the 6-8'-M bicoumarin as sole product (cf. figure). The responsible genes were identified through a bioinformatic approach, cloned and heterologously expressed. It was shown that Saccharomyces cerevisiae transformed with a plasmid carrying the KtnC and DesC genes yielded the same bicoumarines as the wild type Aspergillus sp. The identity and function of the cytochrome P450 enzymes as only mediators of the oxidative phenol coupling of coumarin derivates in Aspergillus sp. was therefore confirmed. The dimerization of siderin is the first example of a highly selective intermolecular oxidative phenol coupling in eukaryotes, which has been elucidated on the enzymatic level and represents the first step towards the generation of a toolbox for biocatalytic application.