HETEROLOGOUS EXPRESSION OF FUNCTIONALLY ACTIVE HUMAN CYTOCHROMES P450.1. SYNTHESIS OF CYTOCHROME P450IID6 BY TRANSFORMED SACCHAROMYCES-CEREVISIAE CELLS

Functionally active human cytochrome P450IID6 was expressed in Sacchar omyces cerevisiae cells transformed with shuttle vectors based on the 2-mu m plasmid and containing cDNA for cytochrome P450IID6. Transcript ion of cDNA was controlled by the regulated PHO5 promoter of yeast aci d phosphatase or by the GAL10-CYC1 regulated chimeric promoter. The tr ansformed yeast cells produced cytochrome P450, as documented by reduc ed CO difference spectra. The transformed yeast cells metabolized a dr ug, namely spartein, yielding products normally formed in the human or ganism. Expression of human cytochrome P450s, involved in metabolism o f xenobiotics, offers a promising approach to the study of new drugs a nd to the screening of genotoxic compounds.