Engineering cytochrome P450 biocatalysts for biotechnology, medicine and bioremediation.
BACKGROUND
Cytochrome P450 enzymes comprise a superfamily of heme monooxygenases that are of considerable interest for the: i) synthesis of novel drugs and drug metabolites; ii) targeted cancer gene therapy; iii) biosensor design; and iv) bioremediation. However, their applications are limited because cytochrome P450, especially mammalian P450 enzymes, show a low turnover rate and stability, and require a complex source of electrons through cytochrome P450 reductase and NADPH.


METHODS
In this review, we discuss the recent progress towards the use of P450 enzymes in a variety of the above-mentioned applications. We also present alternate and cost-effective ways to perform P450-mediated reaction, especially using peroxides. Furthermore, we expand upon the current progress in P450 engineering approaches describing several recent examples that are utilized to enhance heterologous expression, stability, catalytic efficiency and utilization of alternate oxidants.


RESULTS
The review provides a comprehensive knowledge in the design of P450 biocatalysts for potentially practical purposes. Finally, we provide a prospective on the future aspects of P450 engineering and its applications in biotechnology, medicine and bioremediation.


CONCLUSIONS
Because of its wide applications, academic and pharmaceutical researchers, environmental scientists and healthcare providers are expected to gain current knowledge and future prospects of the practical use of P450 biocatalysts.
Kumar
Santosh
S
University of Missouri-Kansas City, School of Pharmacy, Division of Pharmacology and Toxicology, 2464 Charlotte St., Kansas City, MO 64108, USA. kumarsa@umkc.edu
D000818:Animals; D055162:Biocatalysis; D001673:Biodegradation, Environmental; D001698:Biomedical Engineering; D015374:Biosensing Techniques; D001709:Biotechnology; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055808:Drug Discovery; D004800:Enzymes, Immobilized; D015316:Genetic Therapy; D006801:Humans; D015202:Protein Engineering
D004800:Enzymes, Immobilized; D003577:Cytochrome P-450 Enzyme System