Application biotransformation

However poor bioavailability and some adverse effects may have limited their use in medicinal applications. Biotransformation by microbial methods has been used for producing new derivatives, expanding their molecular diversity and... 

Amino acid separations represent another specific application of the technology. Amino acids are important synthesis precursors - in particular for pharmaceuticals -such as, for example, D-phenylglycine or D-parahydroxyphenylglycine in the preparation of semisynthetic penicillins. They are also used for other chiral fine chemicals and for incorporation into modified biologically active peptides. Since the unnatural amino acids cannot be obtained by fermentation or from natural sources, they must be prepared by conventional synthesis followed by racemate resolution, by asymmetric synthesis, or by biotransformation of chiral or prochiral precursors. Thus, amino acids represent an important class of compounds that can benefit from more efficient separations technology. 

Application of the desired biotransformation to give a practical and economical process required high molar conversion yields, high amino transferase activities, highly effident product recovery and an inexpensive source of phenylpyruvic add. With genetic and/or biochemical manipulation considerable progress can be made towards meeting some of these requirements. 

In the following sections we will explain some applications of enzymes (and cells) in the transformation of sterols and steroids. You should realise, however, that for each process a decision has to be made whether to use an enzyme-mediated transformation or to use a chemical reaction. In many instances the biotransformation process is foe most attractive but, as we will see later, this is not always the case. 

In the same text, P. R. Wallnofer and G. Engelhardt have reviewed the application of biotransformation of aromatic and heterocyclic compounds, again describing a wide range of chemical transformation and organisms. 

The oxidation of heteroatoms and, in particular, the conversion of sulfides to asymmetric sulfoxides has continued to be a highly active field in biocatalysis. In particular, the diverse biotransformations at sulfur have received the majority of attention in the area of enzyme-mediated heteroatom oxidation. This is particularly due to the versatile applicability of sulfoxides as chiral auxiliaries in a variety of transformations coupled with facile protocols for the ultimate removal [187]. 

In biotransformation reactions, ILs can act as tunable solvents or immobilizing agents or additives. They can also be coupled to substrates or other reagents (e.g., acylating agents in Hpase-catalyzed transesterifications [62]). Recent examples of chosen applications are presented below. 

Anari MR, Sanchez RI, Bakhtiar R, Franklin RB, Baillie TA. Integration of knowledge-based metabolic predictions with liquid chromatography data-dependent tandem mass spectrometry for drug metabolism studies application to studies on the biotransformation of indinavir. Anal Chem 2004 76 823-32. 

The use of ionic liquids (ILs) to replace organic or aqueous solvents in biocatalysis processes has recently gained much attention and great progress has been accomplished in this area lipase-catalyzed reactions in an IL solvent system have now been established and several examples of biotransformation in this novel reaction medium have also been reported. Recent developments in the application of ILs as solvents in enzymatic reactions are reviewed. 

Attempts have been made to apply the structure-activity concept (Hansch and Leo 1995) to environmental problems, and this has been successfully applied to the rates of hydrolysis of carbamate pesticides (Wolfe et al. 1978), and of esters of chlorinated carboxylic acids (Paris et al. 1984). This has been extended to correlating rates of biotransformation with the structure of the substrates and has been illustrated with a number of single-stage reactions. Clearly, this approach can be refined with the increased understanding of the structure and function of the relevant degradative enzymes. Some examples illustrate the application of this procedure ... 

These results may be viewed in the wider context of interactions between potential ligands of multifunctional xenobiotics and metal cations in aquatic environments and the subtle effects of the oxidation level of cations such as Fe. The Fe status of a bacterial culture has an important influence on synthesis of the redox systems of the cell since many of the electron transport proteins contain Fe. This is not generally evaluated systematically, although the degradation of tetrachloromethane by a strain of Pseudomonas sp. under denitrifying conditions clearly illustrated the adverse effect of Fe on the biotransformation of the substrate (Lewis and Crawford 1993 Tatara et al. 1993). This possibility should therefore be taken into account in the application of such organisms to bioremediation programs. 

Two sections deal briefly with procedures for investigating the pathways used in biodegradation and biotransformation. They cover briefly the application of isotopes, and of nondestructive methods that include NMR, EPR, and x-ray analysis. They should be viewed in the wider context of procedures for evaluating the effectiveness of bioremediation that are covered in Chapter 13 and their application in Chapter 14. 

The degradation of acenaphthene is initiated by benzylic monooxygenation, and the pathway was determined using [l- C]acenaphthene by the isolation of intermediate metabolites (Selifonov et al. 1998). Importantly, the method proved applicable even when only limited biotransformation of the substrates had taken place by partial oxidation. 

Collectively, these results illustrate the value of this procedure for determining the occurrence of biodegradation and biotransformation in natural environments, and their application to assessing the effectiveness of bioremediation. A number of important limitations should be addressed. 

Venisetty RK, Ciddi V (2003) Application of microbial biotransformation for the new drug discovery using natural drugs as substrate. Curr PharmaceutBiotechnol 4 153-167... 

Figure 4.23 Industrial biotransformations points of application for reaction engineering...

Schnell, B., Faber, K. and Kroutil W. (2003) Enzymatic racemisation and its application to synthetic biotransformations. Advanced Synthesis and Catalysis, 345 (6-7), 653-666. 

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