Enzymatic reactions syntheses

Biotransformations are carried out by either whole cells (microbial, plant, or animal) or by isolated enzymes. Both methods have advantages and disadvantages. In general, multistep transformations, such as hydroxylations of steroids, or the synthesis of amino acids, riboflavin, vitamins, and alkaloids that require the presence of several enzymes and cofactors are carried out by whole cells. Simple one- or two-step transformations, on the other hand, are usually carried out by isolated enzymes. Compared to fermentations, enzymatic reactions have a number of advantages including simple instmmentation reduced side reactions, easy control, and product isolation. 

Enzymatic reactions in synthesis of heterocycles 97MI28, 97MI29. 

In the first publication describing the preparative use of an enzymatic reaction in ionic liquids, Erbeldinger et al. reported the use of the protease thermolysin for the synthesis of the dipeptide Z-aspartame (Entry 6) [34]. The reaction rates were comparable to those found in conventional organic solvents such as ethyl acetate. Additionally, the enzyme stability was increased in the ionic liquid. The ionic liquid was recycled several times after the removal of non-converted substrates by extraction with water and product precipitation. Recycling of the enzyme has not been reported. It should be noted, however, that according to the log P concept described in the previous section, ethyl acetate - with a value of 0.68 - may interfere with the pro-... 

Today SCFs are used for natural product extractions, chromatographic separations, pollution prevention, material processing and as solvents for chemical reactions.[75-77] Chemical applications include catalysis, polymerization, enzymatic reactions and organic synthesis. 

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. 

Aldoximes are prepared from aldehydes and hydroxylamine by condensation reaction, and the dehydration reaction of aldoxime is one of the most important methods of nitrile synthesis in organic chemistry." We speculated that it would become one of the most important examples in Green Chemistry if the dehydration reaction could be realized by an enzymatic method, and started studies on a new enzyme, aldoxime dehydratase, and its use in enzymatic nitrile synthesis. Furthermore, we clarified the relationship between aldoxime dehydratase and nitrile-degrading enzymes in the genome of the microorganisms and the physiological role of the enzyme. 

Since the beginning of the 20th century, organic solvents have been used in enzymatic reaction media [30]. Biocatalytic reactions in water-organic biphasic media were first carried out by Cremonesi et al. [31] and by Buckland et al. [32] less than 30 years ago. Their work aimed at the conversion of high concentrations of poorly water soluble components, particularly steroids. Later, biphasic systems were used for enzyme-catalyzed synthesis reactions that were unfavored in water, changing the reaction equilibrium towards the higher yield of the product, such as esters or peptides. 

This report surveys new routes for the synthesis of oligosaccharides, with emphasis on enzymatic reactions, since they offer unique properties, proceeding highly regio-and stereo-selectively in water solution, and generally afford high yields. Summarized... 

It is well known that solvents have a profound effect on protein conformation. It is often beneficial to apply the phenomena to the optimization of enzymatic reactions. For example, in the synthesis of the GABA... 

This final chapter summarizes the enzyme-catalyzed asymmetric reactions and introduces some new developments in the area of asymmetric synthesis. Among the new developments, cooperative asymmetric catalysis is an important theme because it is commonly observed in enzymatic reactions. Understanding cooperative asymmetric catalysis not only makes it possible to design more enan-tioselective asymmetric synthesis reactions but also helps us to understand how mother nature contributes to the world. 

Oligosaccharide syntheses employing enzymatic reactions would in principle greatly benefit from being performed on a polymer support since the support might effectively facilitate isolation of the final product. Presumably, a water-soluble polymeric support will be preferable to any insoluble support since reaction rates could otherwise become too slow. Glycosidases as synthetic enzymes would be the best candidates to study this type of the enzymic approach to oligosaccharide synthesis. 

This chapter discusses the steps involved in the development and design of a new S02 oxidation catalyst VK69, which was introduced to the market in 1996 by Haldor Topsoe. The strategy and many of the methods are generally applicable to heterogeneous fixed bed catalysts, partly to fluid and slurry bed catalysts, and less relevant for homogeneous catalysts as found in organic synthesis and enzymatic reactions. 

Apart from the impressive recent examples given above, however, there has been too little focus thus far on developing a toolkit of chemocatalytic conversions that are as mutually compatible as enzymatic reactions are in nature (presently there are great differences in solvent, temperature, sensitivity to air and moisture, reactants). This confirms in fact the main difference in approach between organic synthesis and biosynthesis organic synthesis employs a maximum diversity in reagents and conditions while biosynthesis exploits subtlety and selectivity from a small range of materials and conditions (Fig. 13.7). 

J. L. Strominger, Enzymatic Reactions in Bacterial Cell Wall Synthesis Sensitive to Penicillins, Cephalosporins, and Other Antibacterial Agents , Antibiotics 1967, 1, 705-713. 

Enzymes may be used either directly for chiral synthesis of the desired enantiomer of the amino acid itself or of a derivative from which it can readily be prepared, or for kinetic resolution. Resolution of a racemate may remove the unwanted enantiomer, leaving the intended product untouched, or else the reaction may release the desired enantiomer from a racemic precursor. In either case the apparent disadvantage is that the process on its own can only yield up to 50% of the target compound. However, in a number of processes the enzyme-catalyzed kinetic resolution is combined with a second process that re-racemizes the unwanted enantiomer. This may be chemical or enzymatic, and in the latter case, the combination of two simultaneous enzymatic reactions can produce a smooth dynamic kinetic resolution leading to 100% yield. 

Reactions catalyzed by enzymes or enzyme systems exhibit far greater specificities than more conventional organic reactions. Among these specificities which enzymatic reactions possess, stereospecificity is one of the most excellent. To overcome the disadvantage of a conventional synthetic process, i.e., the troublesome resolution of a racemic mixture, microbial transformation with enzymes possessing stereospecificities has been appHed to the asymmetric synthesis of optically active substances [1-10]. C3- and C4-synthetic units (synthons, building blocks), such as epichlorohydrin (EP), 2,3-dichloro-l-propanol (2,3-DCP), glycidol (GLD), 3-chloro-l,2-propanediol (3-CPD), 4-chloro-... 

Figure 1.1 illustrates a condensed version of the classical pathway of bile-acid synthesis, a series of 12 enzymatic reactions that convert cholesterol, which is insoluble, into BAs, which are water soluble. The cholesterol is first converted to 7 alpha-hydroxy cholesterol, followed by the series of enzymatic transformations, eventually producing cholic and chenodeoxycholic acids (not all steps shown). The rate-limiting enzyme in this pathway is cholesterol 7 alpha-hydroxylase (CYP 7A1), which originates from microsomal cytochrome P-450 enzymes, expressed only in the liver hepatocytes. 

Tricoordinate phosphorus >P-X compounds containing a suitable leaving group are indispensable in the synthesis of biophosphates and their structural analogues. In contrast to phosphoryl >P(0)-X and thiophosphoryl >P(S)-X, compounds they are spectacularly more reactive in nucleophilic displacements at the phosphorus centre. Westheimer has compared reactions of P compounds with nucleophiles to enzymatic reactions regarding their reactivity [1]. The essential feature of P compounds is their free electron pair with all the structural, stereochemical and mechanistic consequences that follow. P compounds have the structure of a trigonal pyra-... 

The enzymatic reaction chosen for the DCL was protease-catalyzed amide bond synthesis/hydrolysis. This fundamental transformation is... 

The main drawback of the DHAP-dependent aldolases is their strict specificity for the donor substrate. Apart from the scope limitation that this fact represents, DHAP is expensive to be used stoichiometrically in high-scale synthesis, and labile at neutral and basic pH, and therefore its effective concentration decreases over time in enzymatic reaction media, hindering the overall yield of the aldol reaction. In addition, due to the presence of a phosphate group in both DHAP and the... 

In vitro multi-enzyme systems are set up by the combination of enzyme modules including pathway and even pathway-unrelated enzymes. Also, the synthesis of saccharides in combination with de novo enzymatic sugar synthesis can be accomplished. This so-called combinatorial biocatalysis can be performed in sequential reactors or in a one-pot reaction vessel which challenges further reaction engineering for optimization. Even the combination of an enzyme module with a chemical... 

Membrane reactors have been investigated since the 1970s 11). Although membranes can have several functions in a reactor, the most obvious is the separation of reaction components. Initially, the focus has been mainly on polymeric membranes applied in enzymatic reactions, and ultrafiltration of enzymes is commercially applied on a large scale for the synthesis of fine chemicals (e.g., L-methionine) 12). Membrane materials have been improved significantly over those applied initially, and nanofiltration membranes suitable to retain relatively small compounds are now available commercially (e.g., mass cut-off of 400—750 Da). 

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