Towards engineered topogenesis of cytochrome b(5) and P450 for in vivo transformation of xenobiotics.
Nature is endowed with catalysts capable of an unprecedented diversity of biotransformations, beyond the capabilities of synthetic chemistries. In a biotechnological context, there is a growing and emerging need to tap this catalytic potential. CYP (cytochrome P450) represents a superfamily of enzymes capable of a diverse array of catalytic activities. Distinct members are engaged in biosynthetic reactions within many organisms, while others have a role in the detoxification of foreign compounds. The latter substrates include medicines, pollutants, pesticides, carcinogens, perfumes and herbicides, representing considerable applied importance for pharmacology and toxicology. CYPs show a high degree of stereo- and regio-specificity for their reactions, which have wide industrial applications. Recombinant CYPs are commonly expressed as active recombinant cytosolic forms in Escherichia coli. However, selective permeability of E. coli to many substrates and products can cause problems with product recovery when using whole-cell systems. To overcome these problems, we have been developing approaches to facilitate export of functional recombinant haemoproteins to the inner membrane, periplasm and the outer membrane of E. coli. Here, we describe the progress in relation to cytochrome b(5) and CYPs.
Kaderbhai
M A
MA
Institute of Biological Sciences, Cledwyn Building, University of Wales, Aberystwyth SY23 3DD, UK. mak@aber.ac.uk
Kelly
S L
SL
Kaderbhai
N N
NN
D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015786:Cytochromes b5 / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D005818:Genetic Engineering / Q000379:methods; D006418:Heme / Q000378:metabolism; D008954:Models, Biological; D015202:Protein Engineering / Q000379:methods; D015262:Xenobiotics / Q000493:pharmacokinetics*
D015262:Xenobiotics; D006418:Heme; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System