Premas Biotech has launched its suite of recombinant human cytochrome P450 isozymes expressed in Saccharomyces cerevisiae.
The microsomes contain human CYP450 isozyme and human NADPH oxido reductase, therefore offering higher specific activity and performance.
These isozymes will be expressed in yeast, which means that these recombinant human enzymes mimic their native forms and ensures biological and pharmacologically active isoforms.
Premas will be using its proprietary vectors for optimised expression.
Cytochromes P450 (CYP) enzymes are a super family of the principal enzymes that catalyse the metabolism of drugs and other xenobiotics.
Although CYPs are expressed at different levels in various tissues, the liver contains 90 per cent of those CYPs relevant for detoxification.
In contrast to prokaryotic CYPs, the respective eukaryotic CYPs are membrane-bound and are mainly found on the cytosolic side of the endoplasmic reticulum.
The activity of the CYPs depends strongly on the electron transfer from NADPH-dependent cytochrome P450 reductase and cytochrome b5.
NADPH + H+ + O2 + RH ==> NADP+ + H2O + R-OH
During the last 15 years, in vivo experiments using animal models have been replaced by in vitro studies using human enzymes from different sources.
Microsomal preparations from cellular systems, such as liver slices and human hepatocytes, are used to profile novel entities, but have the inherent disadvantage of a predominantly cellular environment consisting of multiple enzymes, cofactors, transporters, and so on, which contributes to multiple signal-to-noise ratios and varying activities as well.
Recombinant expression is advantageous on the basis that the presence of a single enzyme enables for specific applications and read-outs required in drug metabolism and drug-drug interactions.
Premas Biotech has expressed the major human drug metabolising enzymes (DMEs) have been co-expressed along with human NADPH-dependent cytochrome P450 reductase in Saccharomyces cerevisiae (yeast host system).
The yeast, S cerevisiae system, enables efficient expression of complex, multi-subunit proteins along with post-translational processing which mimics human system.