Water Oxidation by a Cytochrome P450: Mechanism and Function of the Reaction

Resource type
Date created
2013
Authors/Contributors
Abstract
P450cam (CYP101A1) is a bacterial monooxygenase that is known to catalyze the oxidation of camphor, the first committed step in camphor degradation, with simultaneous reduction of oxygen (O2). We report that P450cam catalysis is controlled by oxygen levels: at high O2 concentration, P450cam catalyzes the known oxidation reaction, whereas at low O2 concentration the enzyme catalyzes the reduction of camphor to borneol. We confirmed, using 17O and 2H NMR, that the hydrogen atom added to camphor comes from water, which is oxidized to hydrogen peroxide (H2O2). This is the first time a cytochrome P450 has been observed to catalyze oxidation of water to H2O2, a difficult reaction to catalyze due to its high barrier. The reduction of camphor and simultaneous oxidation of water are likely catalyzed by the iron-oxo intermediate of P450cam, and we present a plausible mechanism that accounts for the 1:1 borneol:H2O2 stoichiometry we observed. This reaction has an adaptive value to bacteria that express this camphor catabolism pathway, which requires O2, for two reasons: 1) the borneol and H2O2 mixture generated is toxic to other bacteria and 2) borneol down-regulates the expression of P450cam and its electron transfer partners. Since the reaction described here only occurs under low O2 conditions, the down-regulation only occurs when O2 is scarce.
Document
Published as
Prasad B, Mah DJ, Lewis AR, Plettner E (2013) Water Oxidation by a Cytochrome P450: Mechanism and Function of the Reaction. PLoS ONE 8(4): e61897. doi:10.1371/journal.pone.0061897
Publication title
PLoS ONE
Document title
Water Oxidation by a Cytochrome P450: Mechanism and Function of the Reaction
Date
2013
Volume
8
Issue
4
Publisher DOI
10.1371/journal.pone.0061897
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Copyright is held by the author(s).
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Peer reviewed?
Yes
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Member of collection
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journal.pone_.0061897.pdf 3.63 MB