Mechanism of L-Threonine and L-Lysine Production by Analog-resistant Mutants of Corynebacterium glutamicum

Abstract

Homoserine dehydrogenases and aspartokinases in L-threonine- or L-threonine and L-lysine-producing mutants derived from Corynebacterium glutamicum KY 9159 (Met-) were studied with respect to the sensitivity to the inhibition by end products, L-threonine and L-lysine. The activities of homoserine dehydrogenases in the mutants which produced L-threonine or L-threonine and L-lysine were slightly less susceptible to the inhibition by L-threonine than the activity in the parent strain, KY 9159. The aspartokinases in the threonine-producing mutants, KY 10484 and KY 10230, which were resistant to α-amino-β- hydroxylvaleric acid (AHV, a threonine analog) and more sensitive to thialysine (a lysine analog) than the parent, were sensitive to the concerted feedback inhibition by L-lysine and L-threonine by about the same degree as KY 9159. The aspartokinase in an AHV- and thialysine-resistant mutant, KY 10440, which was derived from KY 10484 and produced about 14mg/ml of L-threonine in a medium containing 10% glucose was less susceptible to the concerted feedback inhibition than KY 10484 or KY 9159, although the activity was still under the feedback control. In the parent strain, L-threonine activated aspartokinase activity in the absence of ammonium sulfate, an activator of the enzyme, but partially inhibited the activity in the presence of the salt. On the other hand, the enzyme of KY 10440 was activated by L-threonine either in the presence or in the absence of the salt. In another AHV- and thialysine-resistant mutant, KY 10251, which was derived from KY 10230 and produced both 9mg/ml of L-threonine and 5.5mg/ml of L-lysine, L-threonine and L lysine simultaneously added hardly inhibited the activity of aspartokinase. Implications of these results are discussed in relation to L-threonine or L-lysine production, AHV or thialysine resistance and regulation of L-threonine biosynthesis in these mutants.