α-Hydroxy-β-keto acid rearrangement–decarboxylation: impact on thiamine diphosphate-dependent enzymatic transformations
| Autor: | Finian J. Leeper, Werner Hummel, Susana L. A. Andrade, Volker Brecht, Sabrina Loschonsky, Patrizia Lehwald, Michael Müller, Maryam Beigi |
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| Rok vydání: | 2013 |
| Předmět: |
chemistry.chemical_classification
Circular dichroism Stereochemistry Decarboxylation Escherichia coli Proteins Pyruvate Oxidase Organic Chemistry Acetaldehyde Substrate (chemistry) Regioselectivity Biochemistry Substrate Specificity chemistry.chemical_compound Enzyme chemistry Biocatalysis Escherichia coli Structural isomer Ketoglutaric Acids Thiamine Thiamine Pyrophosphate Physical and Theoretical Chemistry |
| Zdroj: | Org. Biomol. Chem.. 11:252-256 |
| ISSN: | 1477-0539 1477-0520 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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