Abstract
Hyperthermophiles are a group of microorganisms that have their optimum growth temperature above 80ºC. Most hyperthermophiles belong to Archaea, the third domain of life. Much attention has been paid on their unique metabolic pathways and related enzymes which are not found in Eukarya and Bacteria. During our study on characteristic synthetic pathways of amino acids and phospholipids in hyperthermophilic archaea, we found out that two kinds of NAD(P)+-dependent dehydrogenases functioning as the key enzyme in each synthetic pathway exhibited a novel cofactor-binding mode. One enzyme is homoserine dehydrogense involved in the biosynthetic pathway from aspartate to homoserine, which is a common precursor for the synthesis of three amino acids, methionine, threonine, and isoleucine. The other is glycerol1-phosphate dehydrogenase involved in the synthesis of sn-glycerol-1-phosphate, which is an archaeaspeci¿c glycerophosphate backbone of phospholipids. We analyzed the crystal structures of these enzymes and determined the factors responsible for their cofactor-binding mode. As a result, it became clear that both enzymes exhibited a novel cofactor selectivity. This ¿nding suggests the presence of diversity in the decision mechanism of the cofactor speci¿city for the two NAD(P)+-dependent dehydrogenases. Therefore, future elucidation of the regulatory function of the two kinds of NAD(P)+-dependent dehydrogenases in their related metabolic system is awaited.
