title: Expression of human cytochrome P450 enzymes in yeast and bacteria and relevance to studies on catalytic specificity.
abstract: Heterologous expression systems can be utilized to great advantage in the study of cytochrome P450 (P450) and other enzymes involved in the biotransformation of drugs and other xenobiotics. The list of studies made possible with the technology includes discernment of catalytic specificity, elucidation of structure-activity relationships, and various biophysical measurements. There are advantages and disadvantages to each of the vector systems and choices must be made on the basis of needs. Yeast expression systems were used to establish that different P450 2C enzymes are involved in the hydroxylations of tolbutamide and (S)-mephenytion. P450 3A4 was also expressed in yeast and its very broad catalytic specificity was confirmed. Recently, it has been possible to express P450 3A4 as well as other human and animal P450s in bacteria after slight modification of their 5'-coding sequences.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146.
authors.forename: F P
authors.initials: FP
authors.lastname: Guengerich
authors.forename: E M
authors.initials: EM
authors.lastname: Gillam
authors.forename: S
authors.initials: S
authors.lastname: Ohmori
authors.forename: P
authors.initials: P
authors.lastname: Sandhu
authors.forename: W R
authors.initials: WR
authors.lastname: Brian
authors.forename: M A
authors.initials: MA
authors.lastname: Sari
authors.forename: M
authors.initials: M
authors.lastname: Iwasaki
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli; D006801:Humans; D008969:Molecular Sequence Data; D011994:Recombinant Proteins; D012441:Saccharomyces cerevisiae; D013379:Substrate Specificity
chemical_list: D011994:Recombinant Proteins; D003577:Cytochrome P-450 Enzyme System