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

Chan, Sunney I. and Yu, Steve S.-F. (2008) Controlled Oxidation of Hydrocarbons by the Membrane-Bound Methane Monooxygenase: The Case for a Tricopper Cluster. Accounts of Chemical Research, 41 (8). pp. 969-979. ISSN 0001-4842. https://resolver.caltech.edu/CaltechAUTHORS:20170131-071607269

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Abstract

The growing need for inexpensive methods to convert methane to methanol has sparked considerable interest in methods that catalyze this process. The integral membrane protein particulate methane monooxygenase (pMMO) mediates the facile conversion of methane to methanol in methanotrophic bacteria. Most evidence indicates that pMMO is a multicopper enzyme, and these copper ions support redox, dioxygen, and oxo-transfer chemistry. However, the exact identity of the copper species that mediates the oxo-transfer chemistry remains an area of intense debate. This highly complex enzyme is notoriously difficult to purify because of its instability outside the lipid bilayer and tendency to lose its essential metal cofactors. For this reason, pMMO has resisted both initial identification and subsequent isolation and purification for biochemical and biophysical characterization. In this Account, we describe evidence that pMMO is a multicopper protein. Its unique trinuclear copper cluster mediates dioxygen chemistry and O-atom transfer during alkane hydroxylation. Although a recent crystal structure did not show this tricopper cluster, we provide compelling evidence for such a cluster through redox potentiometry and EPR experiments on the “holo” enzyme in pMMO-enriched membranes. We also identify a site in the structure of pMMO that could accommodate this cluster. A hydrophobic pocket capable of harboring pentane, the enzyme’s largest known substrate, lies adjacent to this site. In addition, we have designed and synthesized model tricopper clusters to provide further chemical evidence that a tricopper cluster mediates the enzyme’s oxo-transfer chemistry. These biomimetic models exhibit similar spectroscopic properties and chemical reactivity to the putative tricopper cluster in pMMO. Based on computational analysis using density functional theory (DFT), triangular tricopper clusters are capable of harnessing a “singlet oxene” upon activation by dioxygen. An oxygen atom is then inserted via a concerted process into the C−H bond of an alkane in the transition state during hydroxylation. The turnover frequency and kinetic isotope effect predicted by DFT show excellent agreement with experimental data.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ar700277nDOIArticle
http://pubs.acs.org/doi/abs/10.1021/ar700277nPublisherArticle
ORCID:
AuthorORCID
Chan, Sunney I.0000-0002-5348-2723
Yu, Steve S.-F.0000-0002-3462-065X
Additional Information:© 2008 American Chemical Society. Received 13 December 2007. Published online 8 July 2008. Published in print 1 August 2008. This work was supported by Academia Sinica and grants from the National Science Council of the Republic China (Grant NSC 95-2113-M-001-046-MY2). We thank Dr. Michael K. Chan (Departments of Chemistry and Biochemistry, The Ohio State University) for helpful discussions on the science as well as the manuscript.
Funders:
Funding AgencyGrant Number
Academia SinicaUNSPECIFIED
National Science Council (Taipei)NSC 95-2113-M-001-046-MY2
Issue or Number:8
Record Number:CaltechAUTHORS:20170131-071607269
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170131-071607269
Official Citation:Controlled Oxidation of Hydrocarbons by the Membrane-Bound Methane Monooxygenase: The Case for a Tricopper Cluster Sunney I. Chan and Steve S.-F. Yu Accounts of Chemical Research 2008 41 (8), 969-979 DOI: 10.1021/ar700277n
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:73840
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:31 Jan 2017 16:03
Last Modified:09 Mar 2020 13:19

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