Escherichia coli D-Malate Dehydrogenase: a Generalist Enzyme Active in the Leucine Biosynthesis Pathway [Microbiology]

August 26th, 2014 by Vorobieva, A. A., Khan, M. S., Soumillion, P.

The enzymes of the β-decarboxylating dehydrogenase superfamily catalyze the oxidative decarboxylation of D-malate-based substrates with various specificities. Here, we show that, besides its natural function affording bacterial growth on D-malate as carbon source, the D-malate dehydrogenase of E. coli (EcDmlA) naturally expressed from its chromosomal gene, is capable of complementing leucine auxotrophy in a leuB- strain lacking the paralogous isopropylmalate dehydrogenase enzyme. To our knowledge, this is the first example of an enzyme that contributes with a physiologically relevant level of activity to two distinct pathways of the core metabolism, while expressed from its chromosomal locus. EcDmlA features relatively high catalytic activity on at least three different substrates (L-(+)-tartrate, D-malate and 3-isopropylmalate). Because of these properties both in vivo and in vitro, EcDmlA may be defined as a generalist enzyme. Phylogenetic analysis highlights an ancient origin of DmlA indicating that the enzyme has maintained its generalist character throughout evolution. We discuss the implication of these findings for protein evolution.