Application

Poster: A Novel, Robust Recombinant Human P450 Biocatalytic SystemPoster: Evaluation of Dry Powder Preparations of Permeabilized Pichia pastoris Cells Expressing Human Cytochrome P450 2D6 Enzyme (CYP2D6) for Drug Metabolite GenerationPoster: Facile Scale-up Biocatalytic Production of P-450 Metabolites Using a Novel Recombinant Human Catalytic SystemPoster: Multi-Cycle Production of Metabolites with human P450 systemsPoster: Rapid identifcation and production of metabolites using CypExpress^™ 2D6m 3A4 and 2C9Poster: Rapid identifcation and production of metabolites using stabilized dried powder (SDP) of human cytochrome P450S (hCYPS) 2D6, 3A4, and 2C9 engineered in yeastPoster: Utilizing a Novel Biocatalytic Human P450 System for the Multi - Cycle Production of Metabolites

Biochem/physiol Actions

Cytochrome P450 enzymes are heme containing monooxygenases which are found primarily in the mammalian liver. They catalyze the oxidative metabolism of xenobiotics. This metabolism is the initial step in the biotransformation and elimination of a wide variety of drugs and environmental pollutants from the body. Ketoconazole, itraconazole, azamulin, troleandomycin and verapamil are inhibitors, whereas rifampin is an inducer of the enzyme. The isozyme CYP3A4 is a major pathway for the invivo conversion of testosterone to 6β-Hydroxytestosterone via hydroxylation.

Cytochrome P450 is a heterogeneous family of isozymes whose primary function is to oxidize small molecules, both as a function of intermediary metabolism (e.g., fatty acids) and to detoxify exogenous compounds like xenobiotics, pollutants and drug molecules. Cytochrome P450 3A4 (CYP3A4) is one of the isoforms of cytochrome P450 (P450s). CYP3A4 oxidizes more than 90% of marketed drugs through various metabolic processes.

Features and Benefits

CypExpress^™ 3A4 is a permeabilized and stabilized dried yeast powder preparation containing full length, unmodified, human CYP 3A4 and recombinant human NADPH oxidoreductase. Using proprietary processes, CypExpress^™ are expressed in Pichia yeast. Following optimal expression, the cells are inactivated, permeabilized and dried to a fine powder. CypExpress^™ retains the cellular mechanisms to provide the P450 enzymes with the energy and cofactors to continue to function for long experiments, and can generate larger amounts of metabolite than mammalian microsomes or other genetically engineered expression systems. It is designed for rapid screening of drug metabolites and for scaling up metabolite generation.

Legal Information

6538 is a trademark of American Type Culture Collection

CypExpress is a trademark of Oxford Biomedical Research

Physical form

Light yellow, very fine powder

Reconstitution

Per Protocol/Variable

Unit Definition

A reaction mixture containing 500 µM testosterone and 100 mg/mL of CypExpress^™ 3A4 will produce 121.9 µM 6b-hydroxytestosterone in 3 hours at 30°C under the conditions described.