Title: Deciphering the oxygen activation mechanism at the CuC site of particulate methane monooxygenase

Authors: Wei Peng, Xiaoyang Qu, Sason Shaik* & Binju Wang*

Abstract: The enzymatic oxidation of methane to methanol was discovered in methanotrophs over 110 years ago. Nevertheless, the mechanism of action of particulate methane monooxygenase (pMMO) remains elusive, especially regarding O₂ activation and the nature of the active species of the enzyme. Here we decipher the catalytic cycle of pMMO in the presence of the physiological reductant duroquinol (DQH₂). We demonstrate that O₂ activation is in fact initiated by a Cu_C(ii)–DQH⁻ species generated by deprotonation of DQH₂. Our simulations capture the exclusive pathway for the sequential formation of the intermediates, Cu_C(ii)−O₂^•−, Cu_C(ii)−OOH⁻ and H₂O₂, along the O₂ reduction pathway. Furthermore, H₂O₂ activation by Cu_C(ii)−DQH⁻ is initiated by dissociation of DQH^• to yield Cu_C(i), followed by Cu_C(i)-catalysed O−O homolysis, en route to the formation of the Cu_C(ii)−O^•− species, which is responsible for C−H oxidations. These findings uncover the important roles of the phenol co-substrate for O₂ activation and help resolve the enigmatic mechanism of pMMO.

Full-Link: https://www.nature.com/articles/s41929-021-00591-4