Electrochemical Assessment of CYP3A4 Catalytic Activity in Bactosomes

• Published in: BioNanoScience Vol. 14; no. 3; pp. 2930 - 2939
• Main Authors: Koroleva, Polina I., Kuzikov, Alexey V., Gilep, Andrei A., Bulko, Tatiana V., Shumyantseva, Victoria V.
• Format: Journal Article
• Language: English
• Published: New York Springer US 2024; Springer Nature B.V
• Subjects: Biological and Medical Physics; Biomaterials; Biophysics; Bioreactors; Catalysis; Catalysts; Catalytic activity; Catalytic converters; Circuits and Systems; Cytochrome; Cytochrome P450; Cytochromes P450; Demethylation; Diclofenac; Electrocatalysis; Electrochemical oxidation; Electrodes; Electrolysis; Engineering; Enzymes; Erythromycin; Hydroxylation; Metabolites; Nanotechnology; Nonsteroidal anti-inflammatory drugs; Substrates; Enzymatic assay; Electrochemical analysis; Bioreactor; Electron transfer; Voltammetry; Screen-printed electrodes; Cytochrome P450 3A4
• ISSN: 2191-1630; 2191-1649
• DOI: 10.1007/s12668-024-01539-1

In this work, we present investigation on the behavior of bactosomes containing human cytochrome CYP3A4 in comparison with recombinant enzyme. The bactosomes were adsorbed on the surface of screen-printed electrodes modified with didodecyldimethylammonium bromide. We have shown that bactosomes are effective bioreactors in the case of drug metabolic electroenzymatic reactions. The electrocatalytic reaction was conducted at a working potential of − 0.50 ÷  − 0.55 V. Drug conversion was registered by means of measuring of formaldehyde as product of N-demethylation reaction of erythromycin and time-dependent electrochemical oxidation of diclofenac during electrolysis at controlled working potential. The efficiencies of electrocatalysis of erythromycin N-demethylation as well-known cytochrome P450 3A4 substrate in the case of bactosomes containing human cytochrome P450 3A4 was 3.5 ± 0.4 times higher in comparison with highly purified cytochrome P450 3A4-electrode as catalyst. The efficiencies of electrocatalysis of diclofenac 5-hydroxylation in the case of bactosomes were 3.1 ± 0.3 times higher than for purified enzyme. Bactosomes are effective electrochemical enzymatic nanobioreactors with a high electroenzymatic efficiency for metabolite production.