Electrochemically Driven Omeprazole Metabolism via Cytochrome P450 Assembled on the Nanocomposites of Ceria Nanoparticles and Graphene

Abstract

Cytochrome P450 enzymes are iron-heme proteins involve in the metabolism of both endogenous and exogenous compounds. Accurate mimicking of the natural metabolic pathways has attracted significant interest in vitro. Herein, a novel bioelectronic platform for drug metabolism catalyzed by cytochrome P450 was successfully constructed. Due to the excellent oxygen buffering property of ceria, and the excellent electrical conductivity and biocompatibility of graphene, CYP2C19 enzyme assembled on the CS/CeNP/RGO modified GC electrode exhibited excellent electrochemical activity, enzymatic activity, and metabolic efficiency toward omeprazole, in which the apparent Michaelis constant Kmapp was calculated to be 8.22 μM, and the catalytic rate constant kcat and catalytic efficiency kcat/Kmapp were calculated to be 5.72 s−1 and 0.696 μM−1 s−1, respectively. With an electrochemically driven way, the as-prepared CYP2C19/CS/CeNP/RGO/GC electrode could be used as an enzymatic reactor for drug metabolism in vitro, the metabolic yield of omeprazole was 17.2% after electrolysis for 4 h when the GC electrode area was about 7.0 mm2, and as a biosensor for omeprazole with high sensitivity of a LOD of 0.42 μM. Therefore, the as-prepared cytochrome P450 electrochemically-driven system can offer us a promising platform for monitoring substrate metabolism, efficient biosensor for toxicity analysis and bioreactor for chemical synthesis.