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Mutated variant of Candida antarctica lipase B in (S)-selective dynamickinetic resolution of secondary alcohols
Stockholm University, Faculty of Science, Department of Organic Chemistry.
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2011 (English)In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 9, no 1, 81-82 p.Article in journal (Refereed) Published
Abstract [en]

An (S)-selective dynamic kinetic resolution of secondaryalcohols, employing a mutated variant of Candida antarcticalipase B (CalB) gave products in 84–88% yield and in 90–97%ee.

Place, publisher, year, edition, pages
2011. Vol. 9, no 1, 81-82 p.
National Category
Chemical Sciences
URN: urn:nbn:se:su:diva-59542DOI: 10.1039/c0ob00748jISI: 000285157600011OAI: diva2:429582
Swedish Research CouncilKnut and Alice Wallenberg Foundation
Available from: 2011-07-05 Created: 2011-07-05 Last updated: 2012-04-02Bibliographically approved
In thesis
1. Enantioselective biotransformations using engineered lipases from Candida antarctica
Open this publication in new window or tab >>Enantioselective biotransformations using engineered lipases from Candida antarctica
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Enzymes are attractive catalysts in organic synthesis since they are efficient, selective and environmentally friendly. A large number of enzyme-catalyzed transformations have been described in the literature. If no natural enzyme can carry out a desirable reaction, one possibility is to modify an existing enzyme by protein engineering and thereby obtain a catalyst with the desired properties. In this thesis, the development of enantioselective enzymes and their use in synthetic applications is described. 

In the first part of this thesis, enantioselective variants of Candida antarctica lipase A (CALA) towards α-substituted p-nitrophenyl esters were developed by directed evolution. A highly selective variant of CALA towards p-nitrophenyl 2-phenylpropanoate was developed by pairwise randomization of amino acid residues close to the active site. The E value of this variant was 276 compared to 3 for the wild type.

An approach where nine residues were altered simultaneously was used to discover another highly enantioselective CALA variant (E = 100) towards an ibuprofen ester. The sterical demands of this substrate made it necessary to vary several residues at the same time in order to reach a variant with improved properties.

In the second part of the thesis, a designed variant of Candida antarctica lipase B (CALB) was employed in kinetic resolution (KR) and dynamic kinetic resolution (DKR) of secondary alcohols. The designed CALB variant (W104A) accepts larger substrates compared to the wild type, and by the application of CALB W104A, the scope of these resolutions was extended.

First, a DKR of phenylalkanols was developed using CALB W104A. An enzymatic resolution was combined with in situ racemization of the substrate, to yield the products in up to 97% ee. Secondly, the KR of diarylmethanols with CALB W104A was developed. By the use of diarylmethanols with two different aryl groups, highly enantioselective transformations were achieved.

Place, publisher, year, edition, pages
Stockholm: Department of Organic Chemistry, Stockholm University, 2012. 55 p.
protein engineering, directed evolution, kinetic resolution, dynamic kinetic resolution, biotransformation, lipase
National Category
Organic Chemistry
Research subject
Organic Chemistry
urn:nbn:se:su:diva-75000 (URN)978-91-7447-468-8 (ISBN)
Public defence
2012-05-11, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)

At the time of the doctoral defense, the following paper was unpublished and had a status as follows:  Paper 5: Submitted.

Available from: 2012-04-19 Created: 2012-04-02 Last updated: 2013-01-14Bibliographically approved

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Engström, KarinBäckvall, Jan-E.
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