Engineering Human-like Drug Metabolism in Bacteria

Drug metabolism is a very important issue in drug research today. As cytochrome P450 enzymes are responsible for drug metabolism in the human liver, bacterial models that produce these enzymes are being looked at as an alternative to current, more expensive and less effective methods to produce drug metabolites. Actinoplanes sp. ATCC 53771, found in soil, can be used to produce metabolites of the drug sirolimus. This research involves finding the DNA sequences that make up the P450 genes in Actinoplanes sp. by optimizing a colony hybridization procedure. A genomic library was screened to identify P450-containing colonies, and the clones were sequenced and compared to P450 genes from other bacteria. These genes can then be cloned and expressed in a more industrially suitable bacterium for the production of P450 enzymes to be used for the study of drug metabolism.