Diversity and regioselectivity of O-methyltransferases catalyzing the formation of O-methylated flavonoids

Flavonoids and their methylated derivatives have immense market potential in the food and biomedical industries due to their multiple beneficial effects, such as antimicrobial, anti-inflammatory, and anticancer activities. The biological synthesis of flavonoids and their derivatives is often accomplished via the use of genetically modified microorganisms to ensure large-scale production. Therefore, it is pivotal to understand the properties of O-methyltransferases (OMTs) that mediate the methylation of flavonoids. However, the properties of these OMTs are governed by their: sources, substrate specificity, amino acid residues in the active sites, and the intricate mechanism. In order to obtain a clue for the selection of suitable OMTs for the biosynthesis of a target methylated flavonoid, we made a comprehensive review of the currently reported results, with a particular focus on their comparative regioselectivity for different flavonoid substrates. Additionally, the possible mechanisms for the diversity of this class of enzymes were explored using molecular simulation technology. Finally, major gaps in our understanding and areas for future studies were discussed. The findings of this study may be useful in selecting genes that encode OMTs and designing enzyme-based processes for synthesizing O-methylated flavonoids.