Towards semisynthetic natural compounds with a biaryl axis: Oxidative phenol coupling in Aspergillus niger
Katharina Gloria Hugentobler1, Michael Müller2
1Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104 Freiburg, Germany; Institut für Biochemie, Biotechnologie und Bioinformatik, Technische Universität Braunschweig, Spielmannstrasse 7, 38106 Braunschweig, Germany.
Abstract:
Regio- and stereoselective phenol coupling is difficult to achieve using synthetic strategies. However, in nature, cytochrome P450 enzyme-mediated routes are employed to achieve complete axial stereo- and regiocontrol in the biosynthesis of compounds with potent bioactivity. Here, we report a synthetic biology approach whereby the bicoumarin metabolic pathway in Aspergillus niger was specifically tailored towards the formation of new coupling products. This strategy represents a manipulation of the bicoumarin pathway in A. niger via interchange of the phenol-coupling biocatalyst and could be applied to other components of the pathway to access a variety of atropisomeric natural product derivatives.
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