Reactions substrate specificity

The NDP phosphohydrolase acts only on 3, 5 - and 2, 5 -nucleoside diphosphates and specifically removes the 3 -(or 2 -) phosphate. This enzyme also differs from the 3 -nucleotidases and PAPS hydrolases from other sources with respect to the nature of the hydrolase reaction, substrate specificity, metal requirements and inhibitors (Tsang and Schiff, 1976b). 

During their investigations. Young and Kerr found that in some instances the nitrones were unstable under the present Lewis acid conditions, making the reaction substrate specific [21]. Kerr and coworkers addressed this in developing a one-pot synthesis, where nitrones were prepared in situ, and subsequently reacted with the cyclopropane in the presence of the Lewis acid to afford the tetrahydro-l,2-oxazines as the cis diastereoisomer exclusively, in yields ranging from 66 to 93%. An example of this is shown in Scheme 10.26 [22a,b]. 

The TK-catalyzed reaction requires the presence of thiamine pyrophosphate and Mg " as cofactors. Although the substrate specificity of the enzyme has not been thoroughly investigated, it has been shown that the enzyme accepts a wide variety of 2-hydroxyaldehydes including D-glyceraldehyde 3-phosphate [591-57-1], D-glyceraldehyde [453-17-8], D-ribose 5-phosphate /47(9(9-2%/7, D-erythrose 4-phosphate and D-erythrose [583-50-6] (139,149—151). 

Perhaps the biggest impact on the practical utilization of enzymes has been the development of nonaqueous enzymology (11,16,33,35). The use of enzymes in nonaqueous media gready expands the scope of suitable transformations, simplifies thek use, and enhances stabiUty. It also provides an easy means of regulation of the substrate specificity and regio- and enantioselectivity of enzymes by changing the reaction medium. 

The rearrangement has been found to be substrate specific. In some cases, the reaction proceeds as described above, i.e. using alkoxide in alcoholic solvent. In other cases, these conditions do not work well, or the reaction has been found to work better under pressure at elevated temperature in alcoholic solvents, in DMSO, DMF," or toluene. Rigorous exclusion of moisture and carbon dioxide is necessary."... 

For less activated substrates, specific tests are desirable. These are available in some cases. Thus Amstutz etal. showed that the reaction of 3-, 6-, and 8-bromoquinolines with piperidine at about 200° produced normal substitution products. 

Step 3 of Figure 29.3 Alcohol Oxidation The /3-hydroxyacyl CoA from step 2 is oxidized to a /3-ketoacyl CoA in a reaction catalyzed by one of a family of L-3-hydroxyacyl-CoA dehydrogenases, which differ in substrate specificity according to the chain length of the acyl group. As in the oxidation of sn-glycerol 3-phosphate to dihydroxyacetone phosphate mentioned at the end of Section 29.2, this alcohol oxidation requires NAD+ as a coenzyme and yields reduced NADH/H+ as by-product. Deprotonation of the hydroxyl group is carried out by a histidine residue at the active site. 

Watanabe, T., and Nakamura, T. (1972). Studies on luciferase from Photobacterium phosphoreum II. Substrate specificity and stoichitometry of the reaction in vitro. J. Biochem. 72 647-653. 

Applications of peroxide formation are underrepresented in chiral synthetic chemistry, most likely owing to the limited stability of such intermediates. Lipoxygenases, as prototype biocatalysts for such reactions, display rather limited substrate specificity. However, interesting functionalizations at allylic positions of unsaturated fatty acids can be realized in high regio- and stereoselectivity, when the enzymatic oxidation is coupled to a chemical or enzymatic reduction process. While early work focused on derivatives of arachidonic acid chemical modifications to the carboxylate moiety are possible, provided that a sufficiently hydrophilic functionality remained. By means of this strategy, chiral diendiols are accessible after hydroperoxide reduction (Scheme 9.12) [103,104]. 

Enzyme preparations from liver or microbial sources were reported to show rather high substrate specificity [76] for the natural phosphorylated acceptor d-(18) but, at much reduced reaction rates, offer a rather broad substrate tolerance for polar, short-chain aldehydes [77-79]. Simple aliphatic or aromatic aldehydes are not converted. Therefore, the aldolase from Escherichia coli has been mutated for improved acceptance of nonphosphorylated and enantiomeric substrates toward facilitated enzymatic syntheses ofboth d- and t-sugars [80,81]. High stereoselectivity of the wild-type enzyme has been utilized in the preparation of compounds (23) / (24) and in a two-step enzymatic synthesis of (22), the N-terminal amino acid portion of nikkomycin antibiotics (Figure 10.12) [82]. 

SUBSTRATE-SPECIFIC REACTIONS OF DIBROMIDES OF a-ARYLI-DENE-BENZOCYCLANONES WITH AZIDE NUCLEOPHILE... 

It is useful to differentiate between substrate specificity, which is the inclination of the given enzyme to react more efficiently with (or, in some cases, bind more tightly to) some potential substrates than others, and product specificity, which is the inclination of the enzyme to transform the substrate into only one (usually) of many possible isomeric products. As a consequence of the principle of microscopic reversibility, for a reversible reaction, product specificity for the reaction in one direction becomes equivalent to substrate specificity in the other direction. 

Often exhibit broad substrate specificity, thus acting on many compounds consequently, different P450s may catalyze formation of the same product Extremely versatile catalysts, perhaps catalyzing about 60 types of reactions... 

Cellulase enzyme complexes consist of three major types of proteins that synergistically catalyze the breakdown of a cellulosic substrate. Because the enzymes are strictly substrate-specific in their action, any change in the structure or accessibility of the substrate can have a considerable influence on the course of the hydrolysis reaction. A pretreatment method based on exposing cellulosic substrate to phosphoric acid solution [9] and addition of the nonionic... 

The substrate specificity of farnesyl pyrophosphate synthetase has been studied using 3-methyl-2-aIkenyl pyrophosphates (90) as models. When (90) bears a large side-chain i.e. R = C4H9), the reaction with isopentenyl pyrophosphate ceases after the formation of (91) and this reaction has been... 

Redmond, T.M. et al.. Identification, expression, and substrate specificity of a mammalian beta-carotene 15,15-dioxygenase, J. Biol. Chem., 276, 6560, 2001. Leuenberger, M.G., Engeloch-Jarret, C., and Woggon, W.D., The reaction mechanism of the enzyme-catalyzed central cleavage of beta-carotene to retinal, Ang. Chem. Int. Ed., 40, 2614, 2001. 

As each BVMO is limited in substrate specificity, it is crucial to have a large collection of these oxidative biocatalysts available. Except for expanding the scope of possible reactions, a large toolbox of BVMOs would also increase the chance of being able to perform any wanted specific chemo-, regio- and/or enantioselective reaction. This contrasts with the present situation as only a relatively small number of BVMOs can be exploited for biocatalytic purposes. Therefore, it is still crucial to discover or engineer BVMOs with novel biocatalytic properties. 

Although the absolute configurations of the products are opposite to that of antiinflammatory active compounds, and the substrate specificity is rather restricted as to the steric bulkiness around the reaction center, the enzyme system of A. bronchisepticus was proved to have a unique reactivity. Thus, detailed studies on the isolated enzyme were expected to elucidate some new interesting mechanism of the new type of decarboxylation. Thus, the enzyme was purified. (The enzyme is now registered as EC 4.1.1.76.) The molecular mass was about 24kDa. The enzyme was named as arylmalonate decarboxylase (AMDase), as the rate of the decarboxylation of phenylmalonic acid was faster than that of the a-methyl derivative. ... 

Substrate specificity and stereochemical source of TKase-catalyzed reaction... 

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