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Tuning and switching enantioselectivity of asymmetric carboligation in an enzyme through mutational analysis of a single hot spot.

08:00 EDT 21st October 2015 | BioPortfolio

Summary of "Tuning and switching enantioselectivity of asymmetric carboligation in an enzyme through mutational analysis of a single hot spot."

Enantioselective bond making and breaking is a hallmark of enzyme action, yet switching the enantioselectivity of an enzymatic reaction is a difficult undertaking and typically requires extensive screening of mutant libraries and introduction of multiple mutations. Here, we demonstrate that mutational diversification of a single catalytic hot spot in the enzyme pyruvate decarboxylase gives access to both enantiomers of acyloins acetoin and phenylacetylcarbinol, important pharmaceutical precursors, in case of acetoin even starting from the unselective wild-type protein. Structural analysis by protein crystallography is used to rationalize these findings and to propose a mechanistic model of how enantioselectivity is controlled. In broader context, our studies highlight the efficiency of mechanism-inspired rational protein design for enhancing and switching enantioselectivity of enzymatic reactions by systematically exploring the biocatalytic potential of a single hot spot.

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Name: Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
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