Guengerich F P, Gillam E M, Ohmori S, Sandhu P, Brian W R, Sari M A, Iwasaki M
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146.
Toxicology. 1993 Oct 5;82(1-3):21-37. doi: 10.1016/0300-483x(93)90057-y.
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.
异源表达系统在细胞色素P450（P450）以及参与药物和其他外源性物质生物转化的其他酶的研究中具有很大的优势。利用该技术开展的研究包括催化特异性的识别、构效关系的阐明以及各种生物物理测量。每种载体系统都有优缺点，必须根据需求做出选择。酵母表达系统被用于确定不同的P450 2C酶参与甲苯磺丁脲和（S）-美芬妥因的羟基化反应。P450 3A4也在酵母中表达，并证实了其非常广泛的催化特异性。最近，在对其5'-编码序列进行轻微修饰后，已能够在细菌中表达P450 3A4以及其他人和动物的P450。
