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Issue 2, 2013
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α-Hydroxy-β-keto acid rearrangement–decarboxylation: impact on thiamine diphosphate-dependent enzymatic transformations

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Abstract

The thiamine diphosphate (ThDP) dependent MenD catalyzes the reaction of α-ketoglutarate with pyruvate to selectively form 4-hydroxy-5-oxohexanoic acid 2, which seems to be inconsistent with the assumed acyl donor role of the physiological substrate α-KG. In contrast the reaction of α-ketoglutarate with acetaldehyde gives exclusively the expected 5-hydroxy-4-oxo regioisomer 1. These reactions were studied by NMR and CD spectroscopy, which revealed that with pyruvate the observed regioselectivity is due to the rearrangement–decarboxylation of the initially formed α-hydroxy-β-keto acid rather than a donor–acceptor substrate role variation. Further experiments with other ThDP-dependent enzymes, YerE, SucA, and CDH, verified that this degenerate decarboxylation can be linked to the reduced enantioselectivity of acyloins often observed in ThDP-dependent enzymatic transformations.

Graphical abstract: α-Hydroxy-β-keto acid rearrangement–decarboxylation: impact on thiamine diphosphate-dependent enzymatic transformations

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The article was received on 11 Oct 2012, accepted on 08 Nov 2012 and first published on 22 Nov 2012


Article type: Communication
DOI: 10.1039/C2OB26981C
Citation: Org. Biomol. Chem., 2013,11, 252-256
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    α-Hydroxy-β-keto acid rearrangement–decarboxylation: impact on thiamine diphosphate-dependent enzymatic transformations

    M. Beigi, S. Loschonsky, P. Lehwald, V. Brecht, S. L. A. Andrade, F. J. Leeper, W. Hummel and M. Müller, Org. Biomol. Chem., 2013, 11, 252
    DOI: 10.1039/C2OB26981C

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