EXPRESSION OF HUMAN CYTOCHROME-P450 ENZYMES IN YEAST AND BACTERIA ANDRELEVANCE TO STUDIES ON CATALYTIC SPECIFICITY

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 sp ecificity, elucidation of structure-activity relationships, and variou s biophysical measurements. There are advantages and disadvantages to each of the vector systems and choices must be made on the basis of ne eds. Yeast expression systems were used to establish that different P4 50 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 t o express P450 3A4 as well as other human and animal P450s in bacteria after slight modification of their 5'-coding sequences.