Most of the intermediates in Fig. are only known from theoretical investigations, which primarily employ density functional theory (DFT). This method is usually sufficiently accurate while also being computationally efficient enough to model both active site and important second-sphere residues (although for some of the intermediates, the DFT methods can be inaccurate, see e.g. ref. 45). Still, even DFT cannot describe the entire LPMO enzyme.