Voltage-driven biocatalysis by membrane-bound liver enzymes

Abstract

Human liver microsomes (HLMs) contain the major drug metabolizing cytochrome P450 (CYP) enzyme, and their redox partner protein, CYP-NADPH reductase (CPR). Due to the broad range of biocatalytic reactions catalyzed by CYP enzymes, chemists have focused on the structure-function, biosensing, and catalytic applications of this unique class of enzymes. For drug development, HLMs are being used as the in vitro system to study drug metabolism, inhibition, isoform and metabolite profiling, biosensing applications, and drug-drug interactions. My research focus is to understand the electrocatalytic pathways of human and bacterial (bactosomes) membrane-bound liver CYP enzymes as a new bioelectronics platform for drug development and biosensing. We designed a biologically active bactosomal film on a self-assembled monolayer surface, and compared the electrocatalytic properties of CYP, CPR, and the combination of these two expressed in bactosomes. In addition, we developed a human liver microsomal bioreactor constructed on carbon nanostructure electrodes for applications in stereoselective drug metabolite synthesis. We extended this carbon nanostructure approach with magnetic nanomaterials to develop sensitive biosensors and volume-efficient electrocatalytic systems. My other short-term project was to utilize electrochemistry to understand meat color attributes based on redox properties of myoglobin from different species studied under various meat relevant pH conditions.