Whole cell detoxification

Metabolic pathways containing dioxygenases in wild-type strains are usually related to detoxification processes upon conversion of aromatic xenobiotics to phenols and catechols, which are more readily excreted. Within such pathways, the intermediate chiral cis-diol is rearomatized by a dihydrodiol-dehydrogenase. While this mild route to catechols is also exploited synthetically [221], the chirality is lost. In the context of asymmetric synthesis, such further biotransformations have to be prevented, which was initially realized by using mutant strains deficient in enzymes responsible for the rearomatization. Today, several dioxygenases with complementary substrate profiles are available, as outlined in Table 9.6. Considering the delicate architecture of these enzyme complexes, recombinant whole-cell-mediated biotransformations are the only option for such conversions. E. coli is preferably used as host and fermentation protocols have been optimized [222,223]. 

Peptides, DNA, and proteins with a function in heavy metal detoxification have also been studied, and even whole cell and in vivo experiments have been carried out on bacteria and mice. 

Because of the presence of the conjugating systems which are important in the detoxification of BaP, the whole cell systems provide a more realistic measurement of activation and detoxification reactions than the corresponding subcellular systems. However, the mechanistic aspects of the formation of epoxides, dihyd-rodiols, and dihydrodiol epoxides are more readily studied in the subcellular systems. 

The latter approach to remove fermentation inhibitors in lignocellulosic hydrolysate using whole cells was also the focus of study of Wierckx et al. (2010). In this study, the bacterium Cupriavidus basilensis HMF14 was identified as a promising detoxification bacterium, as it consumes HMF, furfural, acetic acid, and a wide... 

Host-mediated assay, m the host-mediated assay, target cells cure inoculated into an animal that receives the chemical treatment. The assay can be performed only with cell lines that do not kill and cure not killed by the host. Several chemicals—including AF-2, EMS, DMN, DEN, and MNNG—have been tested in this assay system. These chemicals induce mutations in the direct test or in cell-or microsome-mediated assays. Such studies may be useful in understanding responses—including tissue distribution, activation, detoxification, and elimination of chemicals— in whole animals. 

In all of these test systems, as also in experimentation with animals, the problem of extrapolation to man is always present. In the case of short-term tests, we are generally extrapolating from an effect on more or less naked DNA or, in some cases, a single cell system devoid of the controls and detoxification mechanisms one would find in the whole animal. 

Men ndez, J. De Prado, R. Detoxification of Chlorotoluron-resistant Biotype of Alpecurus Mysuroides. A Comparison between Cell Cultures and Whole Plants. Physiologia Plantarum, 1997, 99, 97. 

Multi-drug resistance associated protein (MRP), member of the ATP binding Cassette transporter proteins, is particularly involved in glutathione-conjugates detoxification. In human bronchial basal cells MRP mRNA immunostaining was observed at the whole plasma membrane (Baf chot et al. 1997). 

---