Expression of human cytochrome P450 enzymes in yeast and bacteria and relevance to studies on catalytic specificity

Toxicology. 1993 Oct 5;82(1-3):21-37. doi: 10.1016/0300-483x(93)90057-y.

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.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Catalysis
  • Cloning, Molecular
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Escherichia coli
  • Humans
  • Molecular Sequence Data
  • Recombinant Proteins
  • Saccharomyces cerevisiae
  • Substrate Specificity

Substances

  • Recombinant Proteins
  • Cytochrome P-450 Enzyme System