The first examples of (S)-2-hydroxyacid dehydrogenases catalyzing the transfer of the pro-4S hydrogen of NADH are found in the archaea

Reduction of 2-oxoacids to the corresponding (S)-2-hydroxyacids is an impor tant transformation in biochemistry. To date all (S)-2-hydroxyacid dehydrog enases belonging to the L-lactate/L-malate dehydrogenase family have been f ound to transfer the pro-4R hydrogen of either NADH or NADPH to C-2 of the 2-oxoacid substrates during their reduction. Here, we report that recombina ntly generated (S)-2-hydroxyacid dehydrogenases present in the methanoarcha ea Methanococcus jannaschii and Methanothermus fervidus use the pro-4S hydr ogen of NADH to reduce a series of 2-oxoacids to the corresponding (S)-2-hy droxyacids. This information as well as the low sequence identity between t hese archaeal enzymes and the L-lactate/L-malate family of enzymes indicate that these enzymes are not evolutionary related and therefore constitute a new class of (S)-2-hydroxyacid dehydrogenases. (C) 2001 Elsevier Science B .V. All rights reserved.