Applications to Enzymatic Reactions

APPLICATIONS TO ENZYMATIC REACTIONS 2.3.1. Active-Site and Protein Models... 

Schullek JR, Butler JH, Ni ZJ, Chen D, Yuan ZY, A high-density screening format for encoded combinatorial libraries assay miniaturization and its application to enzymatic reactions, Anal. Biochem., 246 20-29, 1997. 

Many of the characteristics of a typical homogeneously catalyzed reaction are, I believe, equally applicable to enzymatic reactions. A suitable example is provided by the hydroformylation reaction catalyzed by... 

This chapter reviewed some of our group s contributions to the development and application of QM/MM methods specifically as applied to enzymatic reactions, including the use of sequential MD/QM methods, the use of effective fragment potentials for reaction mechanisms, the development of the new QM/MM interface in Amber, as well as the implementation and optimization of the SCC-DFTB method in the Amber program. This last implementation allows the application of advanced MD and sampling techniques available in Amber to QM/MM problems, as exemplified by the potential and free energy surface surfaces for the reaction catalyzed by the Tripanosoma cruzi enzyme /ram-sialidasc shown here. 

The next section contains the most relevant findings from ONIOM applications to enzymatic systems performed in our group. This is followed by a discussion of the important protein effects and how this information can be used to improve the modeling of enzymatic reactions. 

A more complete list of early applications of QM/MM methods to enzymatic reactions can be found elsewhere [18, 35, 83, 84], Gao [85] has reviewed QM/MM studies of a variety of solution phenomena. QM/MM methods have also been used to study the spectra of small molecules in different solvents [86] and electrochemical properties of photosynthetic reaction centers within a protein environment [87-89], An approach has also been developed for calculation of NMR shielding tensors by use of a QM/ MM method [90]. 

Enzymes can be used in several ways in chromatographic applications to improve selectivity or to enhance the detector response. Applications may involve enzymes with either a broad specificity toward a group of related compounds or a high specificity toward a particular compound. In the field of drug residue analysis, most current applications concern enzymatic reactions taking place in separate reactors incorporated in LC systems before or after the analytical column. Reactors with immobilized enzymes have proven to be suitable in such continuous flow systems. 

Unlike the abovementioned systems, systems based on E. coli do not permit the expression of glycoproteins without enzymatic modification. Instead, enzymatic approaches are employed to attach the targeted glycan to the proteins expressed in the cells. The great benefits of this enzymatic approach are (i) that proteins can be readily produced in E. coli on a far larger scale than in systems based on mammalian, insect, plant or yeast cells and (ii) easy application of enzymatic reactions in vitro. 

In SFE, in situ derivatization of the analytes is sometimes applied in order to facilitate the extraction of target analytes (Hawthorne et al., 1992). Such a procedure leads to improved extraction selectivity. The application of enzymatic reactions is a powerful means to increase further the selectivity in... 

W. (1996) Catalytic racemisation of alcohols applications to enzymatic resolution reactions. Tetrahedron Lett., 37 (42), 7623-7626. 

Selective reduction of ketones to give chiral, nonracemic alcohols is another important application of enzymatic reactions. Reduction of 6.46 with baker s yeast... 

This chapter aims to provide chemists and biotechnologists with an overview of the state of biocatalysis and its application to different reactions in the drug discovery and development process. In Section 16.2, biocatalysts that catalyze different chemical reactions will be introduced. In Section 16.3, selected examples of mulhstep enzymatic reactions will be highlighted. Finally the chapter will be wrapped up with a discussion on current trends and future perspectives. 

This chapter presents the implementaiton and applicable of a QM-MM method for studying enzyme-catalyzed reactions. The application of QM-MM methods to study solution-phase reactions has been reviewed elsewhere [44]. Similiarly, empirical valence bond methods, which have been successfully applied to studying enzymatic reactions by Warshel and coworkers [19,45], are not covered in this chapter. 

CS indicated that the enolate of acetyl-CoA is significantly more stable than the enol or a proton-sharing enolic form and thus do not support the proposal that a low barrier hydrogen bond is involved in catalysis in CS. This study demonstrates the practial application of high level QM-MM studies to the elucidation of mechanistic details of an enzymatic reaction that are otherwise unclear. 

When you crack open a can of Coca Cola or Pepsi, you are tasting some of the fruits of bioohemioal engineering Most nondiet soft drinks sold in the United States are sweetened with high-fruotose oorn syrup (MFCS), a substitute for the natural sugar that oomes from cane and beets. MFCS, produced by an enzymatic reaction, is an example of the suooessful application of chemical engineering principles to bioohemioal synthesis. So successful, in fact, that more than 1.5 billion of MFCS was sold in the United States last year. 

Enhanced thermal stability enlarges the areas of application of protein films. In particular it might be possible to improve the yield of reactors in biotechnological processes based on enzymatic catalysis, by increasing the temperature of the reaction and using enzymes deposited by the LB technique. Nevertheless, a major technical difficulty is that enzyme films must be deposited on suitable supports, such as small spheres, in order to increase the number of enzyme molecules involved in the process, thus providing a better performance of the reactor. An increased surface-to-volume ratio in the case of spheres will increase the number of enzyme molecules in a fixed reactor volume. Moreover, since the major part of known enzymatic reactions is carried out in liquid phase, protein molecules must be attached chemically to the sphere surface in order to prevent their detachment during operation. 

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. 

An IL solvent system is applicable to not only lipase but also other enzymes, though examples are still limited for hpase-catalyzed reaction in a pure IL solvent. But several types of enzymatic reaction or microhe-mediated reaction have been reported in a mixed solvent of IL with water. Howarth reported Baker s yeast reduction of a ketone in a mixed solvent of [hmim] [PFg] with water (10 1) (Fig. 16). Enhanced enantioselectivity was obtained compared to the reaction in a buffer solution, while the chemical yield dropped. 

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