The reduction of 4b leads to spin density accumulated on the atoms of His147 and the planar conformation of the imidazolium ring is broken, showing that rather than reduction of the Cu-hydroperoxo species, we have reduced His147. This is also seen in previous computational studies (with smaller models of the active site). As shown in previous theoretical studies, neither [CuO 2 ] n+ nor [CuOOH] n+ species are sufficiently powerful oxidants to perform HAA at the C1 or C4 position of the substrate. Since our calculations (contrary to ref. 37) show that we are not able to form an oxyl in the O 2 -driven pathway, we conclude that O 2 is not a suitable co-substrate for the cleavage of glycosidic bonds for the investigated LsAA9 LPMO. This concurs with the recent experimental investigation by Brander et al., where no product formation for LsAA9 occurred under anaerobic conditions.