Controlled Oxidation of Hydrocarbons by the Membrane-Bound Methane Monooxygenase: The Case for a Tricopper Cluster (original) (raw)

Alkane Oxidation: Methane Monooxygenases, Related Enzymes, and Their Biomimetics

Chemical Reviews, 2017

Methane monooxygenases (MMOs) mediate the facile conversion of methane into methanol in methanotrophic bacteria with high efficiency under ambient conditions. Because the selective oxidation of methane is extremely challenging, there is considerable interest in understanding how these enzymes carry out this difficult chemistry. The impetus of these efforts is to learn from the microbes to develop a biomimetic catalyst to accomplish the same chemical transformation. Here, we review the progress made over the past two to three decades toward delineating the structures and functions of the catalytic sites in two MMOs: soluble methane monooxygenase (sMMO) and particulate methane monooxygenase (pMMO). sMMO is a water-soluble three-component protein complex consisting of a hydroxylase with a nonheme diiron catalytic site; pMMO is a membrane-bound metalloenzyme with a unique tricopper cluster as the site of hydroxylation. The metal cluster in each of these MMOs harnesses O 2 to functionalize the CH bond using different chemistry. We highlight some of the common basic principles that they share. Finally, the development of functional models of the catalytic sites of MMOs is described. These efforts have culminated in the first successful biomimetic catalyst capable of efficient methane oxidation without overoxidation at room temperature.

Oxidation of methane by a biological dicopper centre

Nature, 2010

Vast world reserves of methane gas are underutilized as a feedstock for the production of liquid fuels and chemicals owing to the lack of economical and sustainable strategies for the selective oxidation of methane to methanol 1 . Current processes to activate the strong C-H bond (104 kcal mol 21 ) in methane require high temperatures, are costly and inefficient, and produce waste 2 . In nature, methanotrophic bacteria perform this reaction under ambient conditions using metalloenzymes called methane monooxygenases (MMOs). MMOs thus provide the optimal model for an efficient, environmentally sound catalyst 3 . There are two types of MMO. Soluble MMO (sMMO) is expressed by several strains of methanotroph under copper-limited conditions and oxidizes methane with a well-characterized catalytic di-iron centre 4 . Particulate MMO (pMMO) is an integral membrane metalloenzyme produced by all methanotrophs and is composed of three subunits, pmoA, pmoB and pmoC, arranged in a trimeric a 3 b 3 c 3 complex 5 . Despite 20 years of research and the availability of two crystal structures, the metal composition and location of the pMMO metal active site are not known. Here we show that pMMO activity is dependent on copper, not iron, and that the copper active site is located in the soluble domains of the pmoB subunit rather than within the membrane. Recombinant soluble fragments of pmoB (spmoB) bind copper and have propylene and methane oxidation activities. Disruption of each copper centre in spmoB by mutagenesis indicates that the active site is a dicopper centre. These findings help resolve the pMMO controversy and provide a promising new approach to developing environmentally friendly C-H oxidation catalysts.

Biomimetic Modeling of the Active Site of Soluble Methane Monooxygenase Hydroxylase (sMMOH)

Soluble methane monooxygenase (sMMO) belongs to a family of metalloproteins called bacterial multicomponent monooxygenases (BMMs), which contain carboxylate-bridged nonheme diiron cores. These sMMO enzymes are of high interest because they utilize readily available molecular oxygen in their energy conversion of methane to methanol in the metabolic system of methanotrophic bacteria. Methane is abundant in natural gas, and if it can be converted to methanol, a liquid form, under mild conditions as in the enzyme, transportation of this energy source to remote areas will be safer and more convenient. Our research group has a long-term interest in developing small molecule synthetic analogs that can mimic both the structure and function of the active site of the hydroxylase component of sMMO (sMMOH). Unfortunately, no ligand system designed to date has been able to achieve this goal. In our further attempt, synthesis of a triptycene-based bis(benzimidazole) diester ligand L3 is discussed in this paper along with its coordination with iron(II) salt and an external carboxylate. Characterization of the diiron(II) complexes was achieved using UV-vis spectrophometric titrations, X-ray diffraction studies, Mössbauer spectroscopy, and IR spectroscopy. Preliminary oxygenation studies of the diiron(II) complexes with molecular oxygen is also included.

Theoretical modeling of the hydroxylation of methane as mediated by the particulate methane monooxygenase

Journal of Inorganic Biochemistry, 2006

We present here the results of density functional theory (DFT) calculations directed toward elucidation of the CAH bond activation mechanism that might be adopted by the particulate methane monooxygenase (pMMO) in the hydroxylation of methane and related small alkanes. In these calculations, we considered three of the most probable models for the transition metal active site mediating the ''oxo-transfer'': (i) the trinuclear copper cluster bis(l 3-oxo)trinuclear copper(II, II, III) complex 1, recently proposed by Chan et

Particulate methane monooxygenase contains only mononuclear copper centers

Science, 2019

How many metals to oxidize methane? Methane is an important fuel, but there are few direct transformations to partially oxidized products. Bacteria use metalloenzymes to catalyze methane oxidation to methanol, a reaction of industrial interest. Understanding the metal sites that enable this reaction may inspire new biomimetic catalysts. Ross et al. used spectroscopic measurements to assign two monocopper sites in the enzyme particulate methane monooxygenase. These results differ in part from previous proposals for the location and nuclearity of the metal sites and will prompt rethinking about how this metalloenzyme catalyzes methane oxidation. Science , this issue p. 566

Insights into the P-to-Q conversion in the catalytic cycle of methane monooxygenase from a synthetic model system

Proceedings of the National Academy of Sciences, 2008

For the catalytic cycle of soluble methane monooxygenase (sMMO), it has been proposed that cleavage of the O-O bond in the (-peroxo)diiron(III) intermediate P gives rise to the diiron(IV) intermediate Q with an Fe2(-O)2 diamond core, which oxidizes methane to methanol. As a model for this conversion, (-oxo)diiron(III) complex 1 ([Fe III 2 (-O)(-O2H3)(L)2] 3؉ , L ‫؍‬ tris(3,5-dimethyl-4-methoxypyridyl-2-methyl)amine) has been treated consecutively with one eq of H 2O2 and one eq of HClO4 to form 3 ([Fe IV 2 (-O)2(L)2] 4؉). In the course of this reaction a new species, 2, can be observed before the protonation step; 2 gives rise to a cationic peak cluster by ESI-MS at m/z 1,399, corresponding to the {[Fe 2O3L2H](OTf)2} ؉ ion in which 1 oxygen atom derives from 1 and the other two originate from H2O2. Mö ssbauer studies of 2 reveal the presence of two distinct, exchange coupled iron(IV) centers, and EXAFS fits indicate a short Fe-O bond at 1.66 Å and an Fe-Fe distance of 3.32 Å. Taken together, the spectroscopic data point to an HO-Fe IV-O-Fe IV ‫؍‬ O core for 2. Protonation of 2 results in the loss of H2O and the formation of 3. Isotope labeling experiments show that the [Fe IV 2 (-O)2] core of 3 can incorporate both oxygen atoms from H2O2. The reactions described here serve as the only biomimetic precedent for the conversion of intermediates P to Q in the sMMO reaction cycle and shed light on how a peroxodiiron(III) unit can transform into an [Fe IV 2 (-O)2] core. diiron(IV) ͉ iron-oxo ͉ Mö ssbauer spectroscopy ͉ nonheme ͉ oxygen activation