57-Isoform cytochromes P450 for bioconversions

• Published in: Enzyme and microbial technology 2007-05, Vol.40 (6), p.1469-1474
• Main Authors: Wiseman, Alan, Lewis, David F.V.
• Format: Article
• Language: English
• Subjects: Aromatase inhibitors; Bioconversions; Biological and medical sciences; Biotechnology; Cytochromes P450; Enzymes; Fundamental and applied biological sciences. Psychology; ROS
• ISSN: 0141-0229; 1879-0909
• DOI: 10.1016/j.enzmictec.2007.01.013

There are likely to be up to 4500 isoforms of CYP in biota, including 57 in human tissues for isoform substrate specificities. These isoforms display differential inhibition by a wide range of biochemical drug-candidates. Drugs are targeted to CYP19 (aromatase) and CYP17 (17α-hydroxylase of sterols). The CYP19 isoform is rate limiting in oestrogen production in the body as it controls the biotransformation of testosterone to oestradiol by aromatisation of steroid ring A. A range of azoles is being developed for treatment of breast cancer by targeting the CYP19 (aromatase) isoform that catalyses the formation of an aromatic ring A as required for the conversion of testosterone to oestradiol. In addition, CYP17 (17α-hydroxylase of pregnenolone and of progesterone) is targeted by a range of drugs for the treatment of prostate cancer. Inhibitor-CYP comparisons are recommended therefore for CYP19 and CYP17 in silico and real-lab so as to continue the development for instance of therapeutic azole inhibitors of CYP19 (aromatase) such as anastrozole, by recognition in silico of quantitative structure/activity relationships (QSARs) between such therapeutic drugs and CYP-utilising pathways.