Daniel A. Kopp

Dioxygen Activation and Methane Hydroxylation by Soluble Methane Monooxygenase: A Tale of Two Irons and Three Proteins

Methanotrophic bacteria are capable of using methane as their sole source of carbon and energy. The first step in methane metabolism, the oxidation of methane to methanol, is catalyzed by a fascinating enzyme system called methane monooxygenase (MMO). The selective oxidation of the very stable C-H bond in methane under ambient conditions is a remarkable feat that has not yet been repeated by synthetic catalysts and has attracted considerable scientific and commercial interest. The best studied MMO is a complex enzyme system that consists of three soluble protein components, all of which are required for efficient catalysis. Dioxygen activation and subsequent methane hydroxylation are catalyzed by a hydroxylase enzyme that contains a non-heme diiron site. A reductase protein accepts electrons from NADH and transfers them to the hydroxylase where they are used for the reductive activation of O2 . The third protein component couples electron and dioxygen consumption with methane oxidation. In this review we examine different aspects of catalysis by the MMO proteins, including the mechanisms of dioxygen activation at the diiron site and substrate hydroxylation by the activated oxygen species. We also discuss the role of complex formation between the different protein components in regulating various aspects of catalysis.

Soluble methane monooxygenase: activation of dioxygen and methane

The mechanisms by which soluble methane monooxygenase uses dioxygen to convert methane selectively to methanol have come into sharp focus. Diverse techniques have clarified subtle details about each step in the reaction, from binding and activating dioxygen, to hydroxylation of alkanes and other substrates, to the electron transfer events required to complete the catalytic cycle.

Aktivierung von Disauerstoff und Hydroxylierung von Methan durch lösliche Methan‐Monooxygenase: eine Geschichte von zwei Eisenatomen und drei Proteinen

Methanotrophe Bakterien nutzen Methan als ausschliesliche Quelle von Kohlenstoff und Energie. Der erste Schritt des Methan-Metabolismus, die Oxidation von Methan zu Methanol, wird von einem faszinierenden Enzymsystem namens Methan-Monooxygenase (MMO) katalysiert. Die selektive Oxidation der auserst stabilen C-H-Bindung von Methan bei Raumtemperatur ist eine Meisterleistung, die bisher mit synthetischen Katalysatoren nicht reproduziert werden konnte und die ein betrachtliches wissenschaftliches wie kommerzielles Interesse geweckt hat. Bei der am besten untersuchten MMO handelt es sich um ein komplexes Enzymsystem aus drei loslichen Proteinkomponenten, die alle fur die effiziente Katalyse erforderlich sind: Eine Hydroxylase mit einer Nichtham-Dieisen-Einheit katalysiert die Aktivierung von Disauerstoff und die nachfolgende Hydroxylierung von Methan; eine Reduktase erhalt Elektronen von NADH und ubertragt sie auf die Hydroxylase, von der sie zur reduktiven Aktivierung von Disauerstoff verwendet werden; die dritte Proteinkomponente verknupft den Elektronen- und Sauerstoffverbrauch mit der Oxidation von Methan. In dieser Ubersicht diskutieren wir einige Aspekte der Katalyse durch die MMO-Proteine und behandeln dabei detailliert Studien zum Mechanismus der Aktivierung von Disauerstoff an der Dieisen-Einheit sowie zur Substrathydroxylierung durch die aktivierte Sauerstoffspezies. Ferner befassen wir uns mit der Rolle, die die Bildung von Komplexen zwischen den Proteinkomponenten bei der Regulierung diverser Aspekte der Katalyse spielt.

Dioxygen Activation and Methane Hydroxylation by Soluble Methane Monooxygenase: A Tale of Two Irons and Three Proteins A list of abbreviations can be found in Section 7.

Methanotrophic bacteria are capable of using methane as their sole source of carbon and energy. The first step in methane metabolism, the oxidation of methane to methanol, is catalyzed by a fascinating enzyme system called methane monooxygenase (MMO). The selective oxidation of the very stable C-H bond in methane under ambient conditions is a remarkable feat that has not yet been repeated by synthetic catalysts and has attracted considerable scientific and commercial interest. The best studied MMO is a complex enzyme system that consists of three soluble protein components, all of which are required for efficient catalysis. Dioxygen activation and subsequent methane hydroxylation are catalyzed by a hydroxylase enzyme that contains a non-heme diiron site. A reductase protein accepts electrons from NADH and transfers them to the hydroxylase where they are used for the reductive activation of O(2). The third protein component couples electron and dioxygen consumption with methane oxidation. In this review we examine different aspects of catalysis by the MMO proteins, including the mechanisms of dioxygen activation at the diiron site and substrate hydroxylation by the activated oxygen species. We also discuss the role of complex formation between the different protein components in regulating various aspects of catalysis.