Leeper Group



Reactions of MenD Maryam Beigi, Sabrina Loschonsky, Patrizia Lehwald, Volker Brecht, Susana L. A. Andrade, Finian J. Leeper, Werner Hummel, and Michael Müller,
"a-Hydroxy-b-keto Acid Rearrangement–Decarboxylation: Impact on Thiamine Diphosphate-Dependent Enzymatic Transformations",
Org. Biomol. Chem., 2013, (11), 252-256. Full Text.

The thiamine diphosphate (ThDP) dependent MenD catalyzes the reaction of a-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 a-KG. In contrast the reaction of a-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 a-hydroxy-b-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.

Previous abstract Next abstract


Department of Chemistry
University of Cambridge