Exploring the potential of xenobiotic-metabolising enzymes as biocatalysts: evolving designer catalysts from polyfunctional cytochrome P450 enzymes.
1. Biological catalysts have the advantage of being able to catalyse chemical reactions with an often exquisite degree of regio- and stereospecificity in contrast with traditional methods of organic synthesis. 2. The cytochrome P450 enzymes involved in human drug metabolism are ideal starting materials for the development of designer biocatalysts by virtue of their catalytic versatility and extreme substrate diversity. Applications can be envisaged in fine chemical synthesis, such as in the pharmaceutical industry and bioremediation. 3. A variety of techniques of enzyme engineering are currently being applied to P450 enzymes to explore their catalytic potential. Although most studies to date have been performed with bacterial P450s, reports are now emerging of work with mammalian forms of the enzymes. 4. The present minireview will explore the rationale and general techniques for redesigning P450s, review the results obtained to date with xenobiotic-metabolising forms and discuss strategies to overcome some of the logistic problems limiting the full exploitation of these enzymes as industrial-scale biocatalysts.
Gillam
Elizabeth M J
EM
School of Biomedical Sciences, Department of Physiology and Pharmacology, The University of Queensland, Brisbane, Queensland, Australia. e.gillam@uq.edu.au
D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D032621:DNA Shuffling; D015195:Drug Design; D006801:Humans; D009154:Mutation; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D015202:Protein Engineering; D013237:Stereoisomerism; D015262:Xenobiotics / Q000378:metabolism*
D004364:Pharmaceutical Preparations; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System