Oxidation reactions are of fundamental importance in nature, and are key transformations in organic synthesis. The development of new processes that employ transition metals as substrate-selective catalysts and stoichiometric environmentally friendly oxidants, such as molecular oxygen or hydrogen peroxide, is one of the most important goals in oxidation chemistry. Direct oxidation of the catalyst by molecular oxygen or hydrogen peroxide is often kinetically unfavored. The use of coupled catalytic systems with electron-transfer mediators (ETMs) usually facilitates the procedures by transporting the electrons from the catalyst to the oxidant along a low-energy pathway, thereby increasing the efficiency of the oxidation and thus complementing the direct oxidation reactions. As a result of the similarities with biological systems, this can be dubbed a biomimetic approach.
The wobble uridine of certain bacterial and mitochondrial tRNAs is modified, at position 5, through an unknown reaction pathway that utilizes the evolutionarily conserved MnmE and GidA proteins. The resulting modification (a methyluridine derivative) plays a critical role in decoding NNG/A codons and reading frame maintenance during mRNA translation. The lack of this tRNA modification produces a pleiotropic phenotype in bacteria and has been associated with mitochondrial encephalomyopathies in humans. In this work, we use in vitro and in vivo approaches to characterize the enzymatic pathway controlled by the Escherichia coli MnmE•GidA complex. Surprisingly, this complex catalyzes two different GTP- and FAD-dependent reactions, which produce 5-aminomethyluridine and 5-carboxymethylamino-methyluridine using ammonium and glycine, respectively, as substrates. In both reactions, methylene-tetrahydrofolate is the most probable source to form the C5-methylene moiety, whereas NADH is dispensable in vitro unless FAD levels are limiting. Our results allow us to reformulate the bacterial MnmE•GidA dependent pathway and propose a novel mechanism for the modification reactions performed by the MnmE and GidA family proteins.
Oxidationsreaktionen sind sowohl in der Natur von grundlegender Bedeutung als auch entscheidende Umwandlungen in der organischen Synthese. Verfahren, die Übergangsmetalle als substratselektive Katalysatoren und umweltfreundliche stöchiometrische Oxidationsmittel wie molekularen Sauerstoff oder Wasserstoffperoxid nutzen, sind daher eines der wichtigsten Ziele in der Oxidationschemie. Die direkte Oxidation des Katalysators durch molekularen Sauerstoff oder Wasserstoffperoxid ist jedoch häufig kinetisch ungünstigt. Gekoppelte Katalysatorsysteme, d. h. solche, an denen Elektronentransfermediatoren (ETMs) beteiligt sind, können einen energiearmen Weg für die Übertragung der Elektronen vom Katalysator auf das Oxidationsmittel bereitstellen. Dies erhöht die Effizienz der Oxidation deutlich und erweitert den Anwendungsbereich direkter Oxidationsreaktionen erheblich. Wegen der Ähnlichkeit mit biologischen Systemen kann diese Herangehensweise als biomimetischer Ansatz bezeichnet werden.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.