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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.
This article was published in the following journal.
Name: Chembiochem : a European journal of chemical biology
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Biochemical identification of mutational changes in a nucleotide sequence.
Gene rearrangement of the B-lymphocyte which results in a substitution in the type of heavy-chain constant region that is expressed. This allows the effector response to change while the antigen binding specificity (variable region) remains the same. The majority of class switching occurs by a DNA recombination event but it also can take place at the level of RNA processing.
Simultaneous task performance, or switching between tasks in a concentrated period of time.
Enzymes that catalyze inversion of the configuration around an asymmetric carbon in a substrate having one (racemase) or more (epimerase) center(s) of asymmetry. (Dorland, 28th ed) EC 5.1.
A cytokine synthesized by T-LYMPHOCYTES that produces proliferation, immunoglobulin isotype switching, and immunoglobulin production by immature B-LYMPHOCYTES. It appears to play a role in regulating inflammatory and immune responses.
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...