A tale of two methane monooxygenases

Abstract

Methane monooxygenase (MMO) enzymes activate O2 for oxidation of methane. Two distinct MMOs exist in nature, a soluble form that uses a diiron active site (sMMO) and a membrane-bound form with a catalytic copper center (pMMO). Understanding the reaction mechanisms of these enzymes is of fundamental importance to biologists and chemists, and is also relevant to the development of new biocatalysts. The sMMO catalytic cycle has been elucidated in detail, including O2 activation intermediates and the nature of the methane-oxidizing species. By contrast, many aspects of pMMO catalysis remain unclear, most notably the nuclearity and molecular details of the copper active site. Here, we review the current state of knowledge for both enzymes, and consider pMMO O2 activation intermediates suggested by computational and synthetic studies in the context of existing biochemical data. Further work is needed on all fronts, with the ultimate goal of understanding how these two remarkable enzymes catalyze a reaction not readily achieved by any other metalloenzyme or biomimetic compound.

A simple synthesis of symmetric phthalocyanines and their respective perfluoro and transition‐metal complexes

“…The metalation was confirmed by powder X-Ray diffraction studies, which show a clear difference between the metal-free H 2 PcH 16 and the metalated MPcH 16 . Figure 3 shows the diffraction patterns for three samples: an H 2 (black), CuPcH 16 (red) prepared via the direct route and CuPcH 16 (blue) made in the two-step method. The inset shows the zoomed-in spectra for the region 2θ = 10-20°D are distinct from those of H 2 PcH 16 .…”

“…Nature excels at evolving complex catalytic systems that can carry out “simple” chemical reactions cleanly and efficiently. The best (and to us chemists, most frustrating) examples are the enzymes nitrogenase and methane monooxygenase, which can fix nitrogen from the air and oxidise methane to methanol under ambient conditions, respectively. Another example is the activation of dioxygen, which is particularly challenging owing to its resonance stabilisation .…”

Chalkophores

“…In Ms. trichosporium OB3b, many periplasmic proteins implicated in copper-related processes are present, including CopC, CopD, DUF461/PCu A C, and Sco1 proteins (71) as well as the so-called copper sponge Csp1 (123) and the uncharacterized protein PmoD (71). Finally, pMMO itself houses a copper active site in the periplasmic portion of the PmoB subunit (55, 124), which is believed to be the final destination of most copper trafficked into methanotroph cells. For siderophores, demetalation can occur in the cytoplasm (e.g., pyochelin; 125) or the periplasm (e.g., pyoverdine; 117), and more work is needed to determine which is the better model for CuMbn copper release.…”

Preparation and Characterisation of a Bis‐μ‐Hydroxo‐NiIII2 Complex

“…Mono‐ and di‐nuclear high valent metal‐oxygen adducts are powerful oxidants and have been invoked to be the key oxidising intermediates in the catalytic cycles of several metalloenzymes, including cytochrome P450 oxidases, Rieske dioxygenases, tyrosinase and methane monooxygenases (MMO, notably able to catalyse the conversion of methane to methanol) . Fascinatingly, recent spectroscopic analyses of the putative active oxidant in soluble methane monooxygenase (sMMO) would suggest that a bis‐μ‐oxo‐Fe IV 2 diamond core is not the active oxidant, but possibly a hydroxide‐bridged diiron entity facilitates CH 4 oxidation .…”