Aspergillus niger is a rich source of oxidative enzymes, which are important for many industrial applications. However, systematic evaluation of their metabolic characteristics is limited. In this study, structure-dependent metabolism of flavones by Aspergillus niger were investigated with synthetic substrates. Metabolic inhibitor studies suggested that cytochrome P450s are the major enzymes in oxidative metabolism. The reactions include ring hydroxylation, O-demethylation, sulfone/sulfoxide formation, and oxidation of alkyls to carboxy groups. Initial oxidative metabolism occurred almost exclusively at 4'-substituents. 4'-Halogenated- and 3',5'-dihalogenated analogues were stable against biodegradation. Hydrophilic flavones were more rapidly metabolized than lipophilic analogues. Molecular widths of the A and B ring were important determinants of the position of metabolic oxidation and biotransformation rate. The structure-metabolism relationship analysis indicates that the shape of the B ring was the most important parameter of biotransformation. The electrostatic environment of the same ring also affected the transformation. Additionally, the results showed that the B ring may preferentially be oriented toward the catalytic center.
Keywords: Aspergillus niger; cytochrome P450; flavone; regioselectivity; structure−metabolism.