Synthesis of 2-(d-Arabino-tetra-hydroxybutyl)pyrazine-5-sulfonic Acid

An efficient method for the isolation of dihydrodipicolinate synthase (DPS)-defective threonine producers from a Br evibacterium strain with feedback-sensitive aspartokinase (AK, Ak^s) was established. After mutagenesis of a strain with AK, No. 70, mutants resistant to α-amino-β- hydroxyvaleric acid were isolated and then selected as to threonine productivity in the presence of diaminopimelic acid. DPS activity in the strains in which the threonine production was inhibited by lysine was found to be absent or reduced to less than 10 % of the level in the parent. On the other hand, the strains in which the production was not inhibited by lysine were conventional threonine producers with feedback-resistant homoserine dehydrogenases (HDs and HD^Rs) and wild type DPS. The HD activities of most of the threonine mutants were also markedly reduced. However, only one mutant lacking DPS, DK330, exhibited an HD level comparable to that in the parent and produced the largest amount of threonine among the threonine producers obtained. The formation of HD and HK in strain DK330 was hardly repressed by the addition of methionine. Under the optimum conditions, strain DK330 produced 12.4 g/1 of threonine, while a typical HD type threonine producer, BK29, produced 9.9 g/1.