Structural diversification of natural substrates modified by the O-methyltransferase AurJ from Fusarium Graminearum.

Aromatic polyketide and phenylpropanoid derivatives are a large class of natural products produced by bacteria, fungi, and plants. The O -methylation is a unique decoration that can increase structural diversity of aromatic compounds and improve their pharmacological properties, but the substrate specificity of O -methyltransferase hinders the discovery of more natural products with O -methylation through biosynthesis. Here, we reported that the O -methyltransferase AurJ from plant pathogenic fungus Fusarium graminearum could methylate a broad range of natural substrates of monocyclic, bicyclic, and tricyclic aromatic precursors, exhibiting excellent substrate tolerance. This finding will partly change our stereotype about the specificity of traditional methyltransferases, and urge us to mine more O-methyltransferases with good substrate tolerance and discover more methylated natural products for drug discovery and development through directed evolution and combinatorial biosynthesis. [Display omitted] • O -methyltransferase AurJ from Fusarium Graminearum could methylate atrochrysone from plants or fungi in vivo and in vitro. • Unlike common methyltransferases, AurJ could methylate a broad range of substrates, showing excellent substrate tolerance. • AurJ exhibited good enzymatic activities on substrates atrochrysone and emodin, and their kinetic parameters were determined. [ABSTRACT FROM AUTHOR]