Theoretical Insights\ninto the Catalytic Oxidation\nof Phenols and Arylamines by Laccases via the Proton-Coupled Electron\nTransfer Mechanism

Laccases play a vital role in the degradation of toxic\nphenolic\nand aromatic amine compounds, generating considerable attention in\necological pollution remediation. However, the distinct mechanism\nof the laccase-catalyzed oxidation of phenols and arylamines remains\nunclear. Here, we examined the catalytic oxidation mechanisms of phenols\nand arylamines by Trametes versicolor (TvL) and Melanocarpus albomyces (MaL)\nlaccases using molecular docking, quantum mechanics (QM), and QM/molecular\nmechanics (QM/MM) calculations. We docked four phenolic substrates,\nincluding 1,2-benzenediol, 2-propenylphenol, 2-methoxyhydroquinone,\nand 2-aminophenol, to TvL and identified their favorable reaction\nconformations, in which Asp206 of TvL plays an important role in binding\nsubstrates to promote the catalytic reactions. Based on the docking\nconformations, the QM and QM/MM calculations revealed that the oxidation\nreactions take place via a proton-coupled electron transfer mechanism,\nwith proton transfer (PT) from the hydroxyl groups of substrates to\nthe side chain of Asp206 and synchronous electron hopping from the\naromatic ring of substrates to the type one copper (T1Cu) of TvL.\nFor the MaL and 2,6-dimethoxyphenol interacting system, the oxidation\nreactions occur through a concerted double-proton-coupled electron\ntransfer mechanism with a water-mediated indirect PT from the hydroxyl\ngroup of substrates to the conserved Glu235 and electron hopping from\nthe substrate to T1Cu at the same time. The corresponding energy barriers\nchange from 0.7 to 18.4 kcal/mol, indicating the different degradation\nrates of the phenols and arylamines by laccases. These findings provide\ninsights into the oxidation mechanism of phenols and arylamines by\nlaccases and may extend the applications of laccases.