Hydrolases synthesis

Table 7.1. What is known (or we think is known) about GA-induced hydrolase synthesis in isolated barley aleurone layers...

Amino acids must be provided for de novo hydrolase synthesis Undisputed... 

The induction of specific acid hydrolase synthesis is the result of (1) a... 

A. Natube and Pathogenesis of Stimulation of Acid Hydrolase Synthesis... 

Ebramination of Table III indicates the character of add hydrolase synthesis as a function of diverse inducer molecules. Of importance is the... 

Dysynchronovs Lysosome-Vacdolar Acid Hydrolase Synthesis Induced by Various Stjmuu... 

Kroutil, W., Osprian, L, Mischitz, M. and Faber, K. (1997b) Chemoenzymatic synthesis of (S)-(-)-frontalin using bacterial epoxide hydrolases. Synthesis, 156-158. 

The antiviral activity of (5)-DHPA in vivo was assessed in mice inoculated intranasaHy with vesicular stomatitis vims ( 5)-DHPA significantly increased survival from the infection. (5)-DHPA did not significantly reduce DNA, RNA, or protein synthesis and is not a substrate for adenosine deaminase of either bacterial or mammalian origin. However, (5)-DHPA strongly inhibits deamination of adenosine and ara-A by adenosine deaminase. Its mode of action may be inhibition of Vadenosyl-L-homocysteine hydrolase (61). Inhibition of SAH hydrolase results in the accumulation of SAH, which is a product inhibitor of Vadenosylmethionine-dependent methylation reactions. Such methylations are required for the maturation of vital mRNA, and hence inhibitors of SAH hydrolase may be expected to block vims repHcation by interference with viral mRNA methylation. 

U. T. Bornscheuer, R. J. Kazlauskas, Hydrolases in Organic Synthesis, Wiley-VCH, Weinheim, 1999. 

For a review on epoxide hydrolases and related enzymes in the context of organic synthesis, see Faber, K. Biotransformations in Organic Chemistry, Springer New York 2004. 

The specificity of enzyme reactions can be altered by varying the solvent system. For example, the addition of water-miscible organic co-solvents may improve the selectivity of hydrolase enzymes. Medium engineering is also important for synthetic reactions performed in pure organic solvents. In such cases, the selectivity of the reaction may depend on the organic solvent used. In non-aqueous solvents, hydrolytic enzymes catalyse the reverse reaction, ie the synthesis of esters and amides. The problem here is the low activity (catalytic power) of many hydrolases in organic solvents, and the unpredictable effects of the amount of water and type of solvent on the rate and selectivity. 

Asano et al. have developed an approach for the synthesis of D-amino acids through DKR using a two-enzyme system [55]. They had previously reported the discovery of new D-stereospecific hydrolases that can be applied to KR of racemic amino acid amides to yield D-amino acids. Combination of a D-stereospedfic hydrolase with an amino acid amide racemase allows performing DKR of i-amino acid amides yielding enantiomerically pure D-amino acids in excellent yields (Figure 4.29). 

In an asymmetric synthesis, the enantiomeric composition of the product remains constant as the reaction proceeds. In practice, ho vever, many enzymatic desymmetrizations undergo a subsequent kinetic resolution as illustrated in Figure 6.5. For instance, hydrolysis of a prochiral diacetate first gives the chiral monoalcohol monoester, but this product is also a substrate for the hydrolase, resulting in the production of... 

The principal methods for the hydrolase-promoted synthesis of enantiomerically pure alcohols are depicted in Figure 6.44. Biocatalytic acylation and alcoholysis have been reviewed recently [116,117]. Lipases, esterases, and proteases catalyze these reactions, but CAL-B [118-120], CRL [121,122], and diverse lipase preparations from Pseudomonas species are common place. 

Chiral epoxides and their corresponding vicinal diols are very important intermediates in asymmetric synthesis [163]. Chiral nonracemic epoxides can be obtained through asymmetric epoxidation using either chemical catalysts [164] or enzymes [165-167]. Biocatalytic epoxidations require sophisticated techniques and have thus far found limited application. An alternative approach is the asymmetric hydrolysis of racemic or meso-epoxides using transition-metal catalysts [168] or biocatalysts [169-174]. Epoxide hydrolases (EHs) (EC 3.3.2.3) catalyze the conversion of epoxides to their corresponding vicinal diols. EHs are cofactor-independent enzymes that are almost ubiquitous in nature. They are usually employed as whole cells or crude... 

Bornscheuer, U.T. and Kazlauskas, R.J. (2006) Hydrolases in Organic Synthesis, 2nd edn Wiley-VCH Verlag GmbH, Weinheim. 

All the transformations described above may be realized using various classes of enzymes. However, the importance for practical applications in organic synthesis is not the same for each class of the six enzyme classes, two are most commonly used hydrolases and oxidoreductases (altogether >85% of the total applications) [1, 3]. 

The activity of carbamoyl phosphate synthase I is determined by A -acetylglutamate, whose steady-state level is dictated by its rate of synthesis from acetyl-CoA and glutamate and its rate of hydrolysis to acetate and glutamate. These reactions are catalyzed by A -acetylglu-tamate synthase and A -acetylglutamate hydrolase, respectively. Major changes in diet can increase the concentrations of individual urea cycle enzymes 10-fold to 20-fold. Starvation, for example, elevates enzyme levels, presumably to cope with the increased production... 

Reviews see (a) Wong, C.-H. Whitesides, G. M. Enzymes in Synthetic Organic Chemistry, Pergamon Oxford, 1994. (b) Bornscheuer, U. T. Kazlauskas, R. J. Hydrolases in Organic Synthesis Regio- and Stereoselective Biotransformations Wiley Chichester, 1999. 

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