Inhibition of Maize Caffeate 3-O-Methyltransferase by Nitecapone as a Possible Approach to Reduce Lignocellulosic Biomass Recalcitrance

Maize (Zea mays) caffeate 3-O-methyltransferase (ZmaysCOMT, EC 2.1.1.68), a key enzyme of the phenylpropanoid pathway, catalyzes theO-methylation of caffeic acid to ferulic acid, a precursor of lignin polymer and a crucial component of the cell wall structure. Plant cell wall recalcitrance is due to lignin, and the discovery of specific inhibitors ofZmaysCOMT could be useful to increase the digestibility of the lignocellulose biomass and improve the production of cellulosic biofuels. In this work, we have modeled the three-dimensional structure ofZmaysCOMT and prospected promising inhibitors by using virtual screening techniques. A set of 1668 putative candidates was screened from a virtual library and docked in the active site of the enzyme, and nitecapone was selected as one of the most promising enzyme inhibitors. Details of the mode of inhibition were assessed by in silico simulation and in vitro assays of nitecapone on the enzyme. In comparison with the nitecapone-free control, kinetics parameters showed different values ofV(max)andK(M), suggesting a kinetic profile such as mixed inhibition of theZmaysCOMT. In brief, we suggest that the nitecapone-induced inhibition ofZmaysCOMT may serve as a non-transgenic strategy to explore the biosynthesis of ferulic acid and lignin, their relationships with the recalcitrance of lignocellulosic biomass, and, possibly, to improve bioethanol production.

Automated summary

Modeling the structure ofZmaysCOMT and screening for potential inhibitors, such as nitecapone, could offer a non-transgenic strategy to explore the biosynthesis of ferulic acid and lignin, potentially improving bioethanol production by affecting lignocellulosic biomass digestibility.