Abstract
Biocatalysis, the conversion of substrates into valuable products by the use of enzymes, has some striking advantages in comparison to standard organic chemistry for drug synthesis. By biocatalysis, substrates that contain several identical reactive groups at different positions can be converted with high regio-selectivity and enantio-selectivity. In this study, an E. coli isolate (E132) was identified which was able to convert the steroid desoxycorticosterone into the product 4-pregnen-20,21-diol-3-one in real terms. The product was purified from the cell culture supernatant by HPLC and its structure was demonstrated by mass spectrometry and NMR spectroscopy. It was tested on inhibition of human 5α-reductases type I and type II. At a concentration of 10 μM, inhibition was 49.0% for type I and 81.8% for type II, whereas there was no inhibition of human aromatase (CYP19) at 20 μM and human 17α-hydroxylase-C17,20-lyase (CYP17) at 2.5 μM detectable. The IC50 value of 4-pregnen-20,21-diol-3-one for human 5α-reductase type II was determined to be 1.56 μM.
Acknowledgements
The authors thank A. Palusczak for excellent technical assistance and K. Hollemeyer and J. Zapp for MS and NMR support, respectively.