title: Optimization of the bacterial cytochrome P450 BM3 system for the production of human drug metabolites.
abstract: Drug metabolism in human liver is a process involving many different enzymes. Among them, a number of cytochromes P450 isoforms catalyze the oxidation of most of the drugs commercially available. Each P450 isoform acts on more than one drug, and one drug may be oxidized by more than one enzyme. As a result, multiple products may be obtained from the same drug, and as the metabolites can be biologically active and may cause adverse drug reactions (ADRs), the metabolic profile of a new drug has to be known before this can be commercialized. Therefore, the metabolites of a certain drug must be identified, synthesized and tested for toxicity. Their synthesis must be in sufficient quantities to be used for metabolic tests. This review focuses on the progresses done in the field of the optimization of a bacterial self-sufficient and efficient cytochrome P450, P450 BM3 from Bacillus megaterium, used for the production of metabolites of human enzymes. The progress made in the improvement of its catalytic performance towards drugs, the substitution of the costly NADPH cofactor and its immobilization and scale-up of the process for industrial application are reported.
authors: Department of Life Sciences and Systems Biology, University of Torino, via Accademia Albertina 13, 10123 Torino, Italy. gianfranco.gilardi@unito.it.
authors: Giovanna
authors: G
authors: Di Nardo
authors: Gianfranco
authors: G
authors: Gilardi
mesh_terms: D000818:Animals; D001410:Bacillus megaterium / Q000201:enzymology*; D001426:Bacterial Proteins / Q000737:chemistry*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D006801:Humans; D008099:Liver / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; C052423:flavocytochrome P450 BM3 monoxygenases