Enzymes in organic synthesis. 22. Effects of organic solvents on horse liver alcohol dehydrogenase-catalyzed reduction

Jones, J. Bryan; Schwartz, Harold

doi:10.1139/v82-051

Cited by 15 publications

(3 citation statements)

References 8 publications

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“…One of the traditional methods used to overcome this drawback is the usage of two phase system in which a co-solvent is be added to raise the substrate solubility in the reaction mixture. [50][51][52][53][54][55][56] This co-solvent can either be water-miscible [57][58][59][60] resulting in a one-phase system or, it can be water-immiscible 50,51,61 leading to an aqueous-organic two-phase system. Table 2 summarizes the effect of solubility of different ketones used in the present study on the enzymatic reduction.…”

Section: Effect Substrate Solubilitymentioning

confidence: 99%

Investigation of asymmetric alcohol dehydrogenase (ADH) reduction of acetophenone derivatives: effect of charge density

et al. 2012

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In an effort to study the effect of substituent groups of the substrate on the alcohol dehydrogenase (ADH) reductions of aryl-alkyl ketones, several derivatives of acetophenone have been evaluated against ADHs from Lactobacillus brevis (LB) and Thermoanaerobacter sp. (T). Interestingly, ketones with non-demanding (neutral) para-substituents were reduced to secondary alcohols by these enzymes in enantiomerically pure form whereas those with demanding (ionizable) substituents could not be reduced. The effect of substrate size, their solubility in the reaction medium, electron donating and withdrawing properties of the ligand and also the electronic charge density distribution on the substrate molecules have been studied and discussed in detail. From the results, it is observed that the electronic charge distribution in the substrate molecules is influencing the orientation of the substrate in the active site of the enzyme and hence the ability to reduce the substrate.

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Section: Effect Substrate Solubilitymentioning

confidence: 99%

Investigation of asymmetric alcohol dehydrogenase (ADH) reduction of acetophenone derivatives: effect of charge density

et al. 2012

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“…Here we show as an example of the dimethyl ether (DME)−water solvent system for the reduction of ketones with alcohol dehydrogenase (ADH) to yield enantiomerically pure alcohols as building blocks for pharmaceuticals. − Reactions with horse liver alcohol dehydrogenase (HL-ADH) in more hydrophobic organic solvents have been investigated by the groups of Jones and Klibanov …”

Section: Introductionmentioning

confidence: 99%

Tunable Solvents for Homogeneous Catalyst Recycle

Lü

Lazzaroni

Hallett

et al. 2004

Ind. Eng. Chem. Res.

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A novel class of tunable solvents facilitates recycle of homogeneous catalysts for both economic and environmental advantages. In a mixed organic-aqueous tunable solvent (OATS), reactions between water-soluble catalysts and moderately hydrophobic substrates can be run homogeneously, with subsequent phase separation for product purification and catalyst reuse. One example demonstrated is the dimethyl ether (DME)-water system, which has been employed as a benign alternative to organic solvents for alcohol dehydrogenase (ADH)-catalyzed reduction of hydrophobic ketones coupled with regeneration of the cofactor NADH. We also show the feasibility of a biphasic DME-water separation scheme to couple with the biocatalytic reaction. The subsequent downstream processing offers the advantages of easily isolating water-insoluble products from the aqueous phase and recycling enzyme-cofactor. Other OATS systems are discussed where the preferential dissolution of modest pressures of CO 2 causes phase separations, which result in very large distribution coefficients of target molecules in the biphasic organicaqueous system, with substantial promise as tunable solvents for biocatalysis.

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“…[1][2][3][4] For industrial applications of ADHs, the use of enzymes in organic solvents is often beneficial and many combinations of ADHs, organic solvents, and substrates have been investigated. [5][6][7][8][9][10][11][12] Although these studies clearly show the utility of organic solvents in enzymatic reactions, the effect of organic solvents on the function of ADHs is not fully understood for various reasons such as (1) ADHs have different solvent-resistance properties, (2) the enzyme activities depend on the organic solvent properties and (3) organic solvents affect co-factor binding and release. 10,[12][13][14][15] Recently, non-covalent interactions between enzymes and small molecules have attracted attention as a new method for modulating the enzyme function.…”

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confidence: 99%

Modulating the catalytic activity and the substrate specificity of alcohol dehydrogenases using cyclic ethers

Kawakami

Hara

Miyamoto

2015

Catal. Sci. Technol.

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The catalytic activities of alcohol dehydrogenases (ADHs) are investigated in the presence of 5% cyclic ethers. Although most cyclic ethers show an inhibitory effect on ADHs, we found that the catalytic rate constant of 2-butanol oxidation by Thermoanaerobacter brockii ADH was increased from 57 to 190 min −1 by the addition of 1,3-dioxolane, which altered the substrate specificity.Alcohol dehydrogenase (ADH) catalyzes the redox interconversion of a variety of alcohols to their corresponding carbonyls coupled with the redox reaction of co-factor NADĲP) + -NAD(P)H. These reactions are catalyzed in the chiral active site of the ADHs; thus, these enzymes are industrially important for the production of optically pure alcohols and kinetic resolution of racemic alcohols. 1-4 For industrial applications of ADHs, the use of enzymes in organic solvents is often beneficial and many combinations of ADHs, organic solvents, and substrates have been investigated. 5-12 Although these studies clearly show the utility of organic solvents in enzymatic reactions, the effect of organic solvents on the function of ADHs is not fully understood for various reasons such as (1) ADHs have different solvent-resistance properties, (2) the enzyme activities depend on the organic solvent properties and (3) organic solvents affect co-factor binding and release. 10,[12][13][14][15] Recently, non-covalent interactions between enzymes and small molecules have attracted attention as a new method for modulating the enzyme function. The catalytic activity of lipases is increased by the addition of fluorinated carboxylic acids, and the substrate specificity and catalytic activity of cytochrome P450s are drastically altered by the addition of various carboxylic acids and organic solvents. 16-21 These methods successfully altered the enzyme functions by the addition of small molecules, avoiding time-consuming mutagenesis techniques. Based on these reports, we expected that the functions of ADHs should also be modulated by organic solvents.Here, we report the effect of organic solvents on the catalytic activities and substrate specificities of three commercially available ADHs, Saccharomyces cerevisiae ADH (ScADH), horse liver ADH (HLADH), and Thermoanaerobacter brockii ADH (TbADH). The substrates were primary and secondary small alcohols (Fig. 1). We selected cyclic ethers as the organic solvents (Fig. 1). Cyclic ethers have relatively high stability and water solubility which make it possible to adjust the concentration of organic solvents in the reaction mixture. In addition, cyclic ethers have a wide variety of structural variations, such as the size of the ether ring, the number and the position of the oxygen atom, and the presence or absence of functional groups, allowing systematic analysis to clarify the effect of organic solvents.We initially investigated the initial velocity of alcohol oxidation reactions normalized by enzyme concentration without organic solvents (Fig. 2). The reaction was monitored at the 340 nm absorption maximum of NAD(P)H...

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Enzymes in organic synthesis. 22. Effects of organic solvents on horse liver alcohol dehydrogenase-catalyzed reduction

Cited by 15 publications

References 8 publications

Investigation of asymmetric alcohol dehydrogenase (ADH) reduction of acetophenone derivatives: effect of charge density

Investigation of asymmetric alcohol dehydrogenase (ADH) reduction of acetophenone derivatives: effect of charge density

Tunable Solvents for Homogeneous Catalyst Recycle

Modulating the catalytic activity and the substrate specificity of alcohol dehydrogenases using cyclic ethers

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