Selective biotransformation

Fitzsimmons, M. E., Collins, J. M., Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome P4503A4 potential contribution to high first-pass metabolism, Drug. Metab. Dispos. 1997, 25, 256-266. 

Fig. 7 Selected biotransformation products of diverse tropane alkaloids identified by LC-MS/MS approaches. Depicted metabolites are only an exert of those presented by Chen et al. for anisodamine (Ada) [6], atropine (Atr) [51], and scopolamine (Sep) [7] as well as by He et al. for benztropine (Benz) [59]. Structures were identified from in vivo and in vitro samples following diverse modes of MS/MS analysis as discussed in the section Biotransformation studies...

Separately living populations of wildlife species may show differences in patterns of environmental contaminants like PCBs. PCB and PCDD/F congener patterns may differ in the same species from various locations as a result of the difference in patterns already present in their (differing) food, as has been demonstrated for seals fed with fish.35 Such differences also relate to selective biotransformation capacities of the organisms involved.20 Large differences in metabolic capacity have been observed between pinnipeds and cetaceans (c/. biotransformation section). This does not only hold for CACs, but also for chlorinated pesticides. For instance, porpoises have been shown to have a... 

Martinkova, L., Klempier, N., Efi-eiml, M., et al. 2002. Selective biotransformation of substituted alicyclic nitriles by Rhodococcus equi A4. Canadain Journal of Chemistry, 80 724—7. 

Selective biotransformations of polyhydroxylated compounds, such as carbohydrates, have been used since some time ago for the activation or protection of some of their hydroxyl groups, allowing different chemical transformations to be carried out without the need for using tedious protection and deprotection steps. Monoesters of some monosaccharides and disaccharides have been obtained using lipases or proteases in polar organic solvents [3]. In addition, the utility of biotransformations in other natural products such as nucleosides [4] or steroids [5] has also been reviewed. 

Selective Biotransformation Potential. A number of factors might limit the possible extrapolation of results to the in vivo situation. Firstly, compounds may be degraded by different cells or mechanisms, e.g. due to acid conditions in the stomach, or by bacterial degradation in the lower parts of the G.I.-tract. Also, other organs may be involved in the biotransformation of a compound, possibly resulting in very specific metabolites. On the other hand, the isolation of hepatocytes results both in the disruption of the typical liver structure, and a selection of cell-types. This may be an important advantage of liver slices, especially now that their preparation has become much easier, faster and more reproducible (20, 21, 22, 23, 24). Last but not least, monolayer... 

Selective biotransformation reactions on D-arabino- and D-threo-hydroxyalk-yltriazoles 01PAC167. 

Selective biotransformation reactions on (i)-benzoxazines 01PAC167. Synthesis and reactions of 2-hetero (RO-, RS- or RR N)-4H-3,l-benzoxazin-4-ones 00JHC1369. 

Rahman, A., K.R. Korzekwa, J. Grogan, F.J. Gonzalez, and J.W. Harris (1994). Selective biotransformation of taxol to 6 alpha-hydroxytaxol by human cytochrome P450 2C8. Cancer Res. 54, 5543-5546. 

Previous sections have illustrated the complexity of most of the compound-specific analyses developed in the environmental field. It is easy then to figure out that the accurate determination of a possible enantiomeric enrichment of chiral pollutants is even more difficult owing to the many co-elution problems and low concentration levels of the analytes. This difficulty could explain the somehow limited research conducted on this topic. However, its interest is clear. Industrial contaminants, such as PCBs or toxafene, are released into the environment as racemates. Therefore, a nonracemic composition of these pollutants might be evidence of selective biotransformation and/or bioaccumulation. Some studies have also pointed to different biological and toxic behaviour for each of the enantiomers [56], something that can be especially relevant for pesticides exhibiting chiral properties. 

HBCD accumulates in soil, sediments and airborne dust, and is rapidly absorbed in the gastrointestinal tract and accumulates in the fatty tissue of organisms, but has a very short hah-life. For example, in fish the half-life of HBCD is only one day. Representation of the individual isomers in the sediments reflects the compositions of commercial mixtures, while the tissues of aquatic animals, especially fish, have a quite different composition of isomers. The dominant substance is the a-isomer the y-isomer is present in much smaller amounts and the content of the fl-isomer remains virtually constant, which can be explained by the almost selective biotransformation of the y-isomer to the a-isomer. 

It is in addressing the need for high selertivity that the recombinant enz5me comes of age to yield a selective biotransformation based on a single, expressed recombinant enzyme Furthermore, recombinant enzymes can be evolved to incorporate improvements in selectivity, stability, and reartion rate to meet the demanding needs of commercial processes. The chapter will now focus on recombinant systems, including engineered recombinant CREDs. 

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