Homoserine Dehydrogenase of Rhodospirillum rubrum

Homoserine dehydrogenase catalyzes the reductive conversion of aspartate P-semialdehyde to homoserine (l), which has been identified in several microorganisms as a precursor of three other amino acids. On the one hand, homoserine is converted to methionine, and through a separate sequence of reactions is transformed to threonine, a precursor of isoleucine (2). Recent studies (3-7) have provided evidence that homoserine dehydrogenase is one of the focal points in control of biosynthesis of the amino acids noted, and that its activity is subject to regulation through several different mechanisms. Feedback inhibition of dehydrogenase activity by threonine appears to be a common feature of these mechanisms, but more complex cont,rols may operate as indicated, by studies with the enzyme from’ the photosynthetic bacterium Rhodospirillum rubrum,. Inhibition of activity of this enzyme by L-threonine is reversed by L-isoleucine and L-methionine, ultimate end products of the biosynthetic pathway under consideration (5, 7). Furthermore, in the absence of the inhibitor, the latter amino acids individually cause significant stimulation of the enzymatic reaction (7, 8). In this report, the general properties of highly purified R. rubrum homoserine dehydrogenase are described, with particular reference to the effects of feedback modifiers on the kinetic behavior of the enzyme. In addition, conditions are specified for demonstration of reversible “desensitization” of the enzyme with respect to such modifiers.