Homoserine dehydrogenase

Aspartate kinase [EC 2.T.2.4], also known as asparto-kinase, catalyzes the reaction of aspartate with ATP to produce 4-phosphoaspartate and ADP. The enzyme isolated from E. coli is a multifunctional protein, also exhibiting the ability to catalyze the reaction of homoserine with NAD(P) to produce aspartate 4-semialdehyde and NAD(P)H (that is, the activity of homoserine dehydrogenase, EC 1.1.1.3). 

CYSTATHIONINE y-LYASE HOMOSERINE DEHYDROGENASE ASPARTATE KINASE HOMOSERINE SUCCINYLTRANSFERASE HomotopIc,... 

GLYOXYLATE REDUCTASE HISTIDINOL DEHYDROGENASE HOMOISOCITRATE DEHYDROGENASE HOMOSERINE DEHYDROGENASE HYDROGEN DEHYDROGENASE... 

ATP -I- L-aspartate = ADP -I- 4-phospho-L-aspartate (The enzyme from E. coli is a multifunctional protein, which also catalyses the reaction of EC 1.1.1.3 homoserine dehydrogenase)... 

Starnes, W.L. Munk, P. Maul, S.B. Cunningham, G.N. Cox, D.J. Shive, W. Threonine-sensitive aspartokinase-homoserine dehydrogenase complex, amino acid composition, molecular weight, and subunit composition of the complex. Biochemistry, 11, 677-687 (1972)... 

Veron, M. Falcoz-Kelly E Cohen, G.N. The threonine-sensitive homoserine dehydrogenase and aspartokinase activities of Escherichia coli K12. The two catalytic activities are carried by two independent regions of the polypeptide chain. Eur. J. Biochem., 28, 520-527 (1972)... 

Azevedo, R.A. Smith, R.J. Lea, P.J. Aspartate kinase regulation in maize Evidence for co-purification of threonine-sensitive aspartate kinase and homoserine dehydrogenase. Phytochemistry, 31, 3731-3734 (1992)... 

Paris, S. Wessel, P.M. Dumas, R. Overproduction, purification, and characterization of recombinant bifunctional threonine-sensitive aspartate kinase-homoserine dehydrogenase from Arabidopsis thaliana. Protein Expr. Purif., 24, 105-110 (2002)... 

Paris, S. Viemon, C. Curien, G. Dumas, R. Mechanism of control of Arabidopsis thaliana aspartate kinase-homoserine dehydrogenase by threonine. J. Biol. Chem., 278, 5361-5366 (2003)... 

Overproduction of E (isoleucine) inhibits enzyme E6 (threonine deaminase), and the consequent rise of D (threonine) reduces the rate of production of C (homoserine) via enzyme E3 (homoserine dehydrogenase). The concentration of B (aspartate semialdehyde) rises, and this in turn inhibits Ej (aspartokinase). It is therefore obvious why the control system is called a negative feedback network, or sequential feedback system. 

As mentioned earlier, L-threonine production can be enhanced by engineering the export or uptake system. An efficient L-threonine producer strain of E. coli KY10935, which was derived from the wild-type strain by multiple rounds of random mutation and selection, was able to produce 100 g L-1 L-threonine after 77 h cultivation [53]. In this strain, the two key enzymes in the L-threonine biosynthesis (homoserine dehydrogenase and homoserine kinase) were identified to be still inhibited by much lower intracellular concentrations of L-threonine than... 

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. 

E. Coli homoserine dehydrogenase none 270,000 ammo 140,000 Kempner et al. (1980)... 

Aspartic Semialdehyde + NADPH + H+ <=> Homoserine + NADP+ (catalyzed by homoserine dehydrogenase). 

In E. coli there are three aspartokinases that catalyze the conversion of aspartate to p-aspartyl phosphate. All three catalyze the same reaction, but they have very different regulatory properties, as is indicated in Fig. 24-13. Each enzyme is responsive to a different set of end products. The same is true for the two aspartate semialdehyde reductases which catalyze the third step. Both repression of transcription and feedback inhibition of the enzymes are involved. Two of the aspartokinases of E. coli are parts of bifimctional enzymes, which also contain the homoserine dehydrogenases that are needed to reduce aspartate semialdehyde in the third step. These aspar-tokinase-homoserine dehydrogenases 1 and 11 (Fig. 

---