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The temperature dependence of enzymatic kinetic resolutions reveals the relative contribution of enthalpy and entropy to enzymatic enantioselectivity
KTH, Superseded Departments, Biotechnology.
KTH, Superseded Departments, Biotechnology.
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1999 (English)In: Biocatalysis and Biotransformation, ISSN 1024-2422, E-ISSN 1029-2446, Vol. 17, no 1, 61-79 p.Article in journal (Refereed) Published
Abstract [en]

The temperature dependence of the enantioselectivity of several lipase-calalyzed hydrolysis and acylation reactions of racemic esters and alcohols has been determined. From the results we estimated the difference in activation enthalpy (Delta Delta H-# and activation entropy (Delta Delta S-#) for the two enantiomers in the enantioselective reaction step. Contrary to earlier suggestions, we found that the enthalpic and entropic contributions to the enantioselectivity are of similar magnitude. A plot of Delta Delta H-# versus Delta Delta S-#-values of data available in the literature for various enzyme-substrate combinations revealed a tempting correlation between the enthalpic and entropic contributions. This observation would imply enthalpy-entropy compensation to be a general feature of enantioselective enzymatic catalysis. On closer inspection of the data set it was realized that this trend must be considered fortuitous. It originates from the non-random collection of those enzyme-substrate combinations for which the numerical value of the enantiomeric ratio can be measured with a suitable degree of accuracy at ambient temperatures. Indications for the occurrence of genuine enthalpy-entropy compensation, however, have been observed for series of homologous substrates and changes of solvent composition.

Place, publisher, year, edition, pages
1999. Vol. 17, no 1, 61-79 p.
National Category
Industrial Biotechnology
Identifiers
URN: urn:nbn:se:kth:diva-13386ISI: 000080165300006OAI: oai:DiVA.org:kth-13386DiVA: diva2:324820
Note
QC 20100616Available from: 2010-06-16 Created: 2010-06-16 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Enthalpy and Entropy in Enzyme Catalysis: A Study of Lipase Enantioselectivity
Open this publication in new window or tab >>Enthalpy and Entropy in Enzyme Catalysis: A Study of Lipase Enantioselectivity
2001 (English)Doctoral thesis, comprehensive summary (Other scientific)
Abstract [en]

Biocatalysis has become a popular technique in organic synthesis due to high activity and selectivity of enzyme catalyzed reactions. Enantioselectivity is a particularly attractive enzyme property, which is utilized for the production of enantiopure substances. Determination of the temperature dependence of enzyme enantioselectivity allows for thermodynamic analyses that reveal the contribution of differential activation enthalpy, ΔR-SΔH, and entropy, ΔR-SΔS. In the present investigation the influence of substrate structure, variations on enzyme structure and of reaction media on the enantioselectivity of Candida Antarctica lipase B has been studied.

The contribution of enthalpy, ΔR-SΔH, and entropy, TΔR-SΔS, to the differential free energy, ΔR-SΔG, of kinetic resolutions of sec-alcohols were of similar magnitude. Generally the two terms were counteracting, meaning that the enantiomer favored by enthalpy was disfavored by entropy. 3-Hexanol was an exception where the preferred enantiomer was favored both by enthalpy and by entropy. Resolution of 1-bromo-2-butanol revealed non-steric interactions to influence both ΔR-SΔH and ΔR-SΔS. Molecular modeling of the spatial freedom of the enzyme-substrate transition state indicated correlation tothe transition state entropy. The acyl chain length was shown to affect enantioselectivity in transesterifications of a sec-alcohol.

Point mutations in the active site were found to decrease or increase enantioselectivity. The changes were caused by partly compensatory changes in both ΔR-SΔH and ΔR-SΔS. Studies on single and double mutation variants showed that the observed changes were not additive.

Enantioselectivity was strongly affected by the reaction media. Transesterifications of a sec-alcohol catalyzed by Candida Antarctica lipase B was studied in eight liquidorganic solvents and supercritical carbon dioxide. A correlation of enantioselectivity and the molecular volume of the solvent was found.

Differential activation enthalpy, ΔR-SΔH, and entropy, ΔR-SΔS, display a compensatory nature. However this compensation is not perfect, which allows for modifications of enantioselectivity. The components of the thermodynamic parameters are highly complex and interdependent but if their roles are elucidated rational design of enantioselective enzymatic processes may be possible.

 

 

Place, publisher, year, edition, pages
Stockholm: KTH, 2001. [10], 49 p.
Keyword
Biocatalysis, enzyme catalysis, Candida antarctica lipase B, enantioselectivity, enthalpy, entropy, CALB, enantiomeric ratio
National Category
Industrial Biotechnology
Identifiers
urn:nbn:se:kth:diva-3216 (URN)91-7283-157-X (ISBN)
Public defence
2001-09-28, 00:00
Note
QC 20100616Available from: 2001-09-12 Created: 2001-09-12 Last updated: 2010-07-22Bibliographically approved

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