Towards semisynthetic natural compounds with a biaryl axis: Oxidative phenol coupling in Aspergillus niger

Bioorg Med Chem. 2018 Apr 1;26(7):1374-1377. doi: 10.1016/j.bmc.2017.08.008. Epub 2017 Aug 31.


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.

Keywords: Atropisomers; Coumarins; Fungal gene expression; Natural compounds; Oxidative phenol coupling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus niger / chemistry*
  • Biological Products / chemical synthesis*
  • Biological Products / chemistry
  • Molecular Structure
  • Oxidation-Reduction
  • Phenols / chemical synthesis*
  • Phenols / chemistry


  • Biological Products
  • Phenols