Novel cytochromes P450 applications arising from the directed-evolution of recombinant micro-organisms


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Abstract

AimsDirected (forced) evolution of cytochromes P450 (overall 2700 CYP isoforms in non-recombinant biota) is a method that has been investigated in yeasts (and other micro-organisms) by aerobically growing brewers' yeast Saccharomyces cerevisiae in very high glucose (20%) media.Methods and ResultsMitochondrial repression subverts cytochrome oxidase biosynthesis into manifest cytochromes P450 accumulation in brewers' yeast. A similar phenomenon is observed with the acridine-induced petit mutant. Cytochromes P450 EC 1·14·14·1 (and mimics) display a range of redox iron-mediated bioconversions in food processing, with mixed function oxidase (O2:mono-oxygenase) intervention results. Unfortunately these enzymes generate reactive oxygen species (ROS) through redox electron recycling, whilst isoform CYP 1A1 can activate precarcinogens such as benzo(a)pyrene to the ultimate (proximate) carcinogen that binds to nuclear DNA.ConclusionsIn conclusion, another 5000 CYP isoforms, for example, might be identified in micro-organisms and many more made to order through recombinant DNA technology and utilized both in vitro and in vivo for aimed bioconversions in industry and in the environment, as part of the impact of greener-approach supporting strategies to minimize global pollution.

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