We have compared the substrate oxidation mechanisms of LPMOs driven by either H 2 O 2 or O 2 using QM/MM calculations on the LsAA9 LPMO. Previous calculations have chosen rather different QM regions leading to a great variety of results in the literature. Here we employ an extended QM region including all important residues. In particular, we included the highly conserved residues His147 and Gln162. These two residues were not consistently included in the QM region in previous studies and are likely a cause for some of the differences.