Homoserine dehydrogenase threonine insensitive

Auxotrophic mutants of L-lysine, diaminopimelate, or L-methionine were found to produce L-threonine in the culture medium, but the amount was not high enough to justify their use in practical production. A resistant mutant to an L-threonine analogue, a-amino-P-hydroxyvaleric acid (AHV), was obtained and shown to be an L-threonine producer. In this strain, homoserine dehydrogenase was insensitive to the feedback inhibition by L-threonine (O Fig. 4.8). The much stronger L-threonine-producing strains were obtained by the combination of the auxotrophic mutations and AHV-resistant mutation. 

The pathway of biosynthesis of L-lysine and L-threonine in Corynebacterium glutamicum is shown in Fig. 1. The first step, the formation of phosphoaspartate from aspartate, is catalyzed by aspertokinase and this enzyme is susceptible to the concerted feedback inhibition by L-lysine and L-threonine. The auxotrophic mutant of homoserine (or threonine plus methionine), lacking homoserine dehydrogenase, was constructed and found to produce L-lysine in the culture medium. Second, the mutants which show the threonine or methionine sensitive phenotype caused by the mutation on homoserine dehydrogenase (low activity) was also found to produce appreciable amounts of L-lysine in the culture medium. Furthermore, a lysine analogue (S-aminoethylcysteine) resistant mutant was obtained as an L-lysine producer and in this strain aspartokinase was insensitive to the feedback inhibition. 

---