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Reversed enantiopreference of Candida rugosa lipase supports different modes of binding enantiomers of a chiral acyl donor
KTH, School of Biotechnology (BIO), Biochemistry.ORCID iD: 0000-0002-9577-832X
1998 (English)In: Journal of Molecular Catalysis - B Enzymatic, ISSN 13811177 (ISSN), Vol. 5, no 1-4, 283-287 p.Article in journal (Refereed) Published
Abstract [en]

Molecular modelling identifies two different productive modes of binding the enantiomers of a 2-methyldecanoic acid ester to the active site of Candida rugosa lipase (CRL). The fast reacting S-enantiomer occupies the previously identified acyl-binding tunnel of the enzyme, whereas the R- enantiomer leaves the tunnel empty. The modelling suggested that if both enantiomers were forced to bind to the active site leaving the tunnel empty, the enzyme would reverse its enantiopreference to become R-enantioselective. To test this hypothesis, we designed a structural analogue to 2- methyldecanoic acid, 2-methyl-6-(2-thienyl)hexanoic acid, which was expected to be too bulky to fit its acyl moiety into the acyl-binding tunnel. The CRL- catalysed hydrolysis of the ethyl ester of this substrate resulted in the preferential conversion of the R-enantiomer as predicted by molecular modelling. This represents the first kinetic evidence supporting the existence of two different modes of binding the enantiomers of a 2- methyldecanoic acid ester to the active site of CRL. We have shown that a rational 3D based approach in combination with substrate engineering can be used to predict and control the stereochemical outcome of a lipase catalysed reaction.

Place, publisher, year, edition, pages
1998. Vol. 5, no 1-4, 283-287 p.
Keyword [en]
2-Methylalkanoic acid, Candida rugosa lipase, Chiral recognition, Enantiopreference, Enantioselective inhibition, Kinetic resolution, Reversed enantioselectivity, alkanoic acid, carboxylic acid derivative, decanoic acid derivative, ester, fungal protein, triacylglycerol lipase, candida, candida rugosa, catalysis, chirality, conference paper, enantiomer, enzyme activity, enzyme kinetics, enzyme substrate, nonhuman, stereochemistry
National Category
Biocatalysis and Enzyme Technology
URN: urn:nbn:se:kth:diva-74864DOI: 10.1016/S1381-1177(98)00095-2OAI: diva2:490131
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