The screening of selected microorganisms for use as models of mammalian drug metabolism.
Fifty fungi and two Streptomyces species were screened for their ability to metabolise the probe substrates aminopyrine, diazepam, testosterone, theophylline and warfarin. The metabolism of the 14C-labelled substrates by whole growing cells was compared with that by rat liver microsomes using TLC-autoradiography. Testosterone, warfarin and diazepam were readily metabolised by most microorganisms, and aminopyrine and theophylline were only metabolised by a few. A relationship between substrate lipophilicity and number of microorganisms able to biotransform the substrate was observed, lipophilic substrates being favoured for metabolism, analagous to mammalian cytochrome P-450. A wide variety of metabolites were produced by the screened cultures, with a significant number co-chromatographing with mammalian metabolites. Most microorganisms appeared to exhibit cytochrome P-450-type oxidative reactions such as hydroxylation and N-demethylation, similar to mammalian hepatic microsomal cytochrome P-450 systems.
Cranfield Biotechnology Centre, Cranfield Institute of Technology, Bedfordshire, UK.
D A
DA
Griffiths
D J
DJ
Best
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Jezequel
D000818:Animals; D003975:Diazepam / Q000378:metabolism; D005658:Fungi / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D013302:Streptomyces / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism; D013806:Theophylline / Q000378:metabolism; D014859:Warfarin / Q000378:metabolism
D004364:Pharmaceutical Preparations; D013739:Testosterone; D014859:Warfarin; D013806:Theophylline; D003975:Diazepam