Threonine biosynthesis

L-Threonine is one of the three major amino acids produced by fermentation processes [45]. Currently, more than 4,000 tons of L-threonine are produced annually by fermentation [46]. In this section, we examine the L-threonine biosynthetic pathway and its regulation, and discuss how the carbon flux can be maximized towards L-threonine biosynthesis by metabolic engineering. The detailed description on L-threonine biosynthetic pathways and regulations involved is shown in Fig. 1. 

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... 

TS is a fold-type II PLP-dependent enzymes, which catalyzes the ultimate step in threonine biosynthesis, the... 

Fig. 2. Threonine biosynthesis. The successive chemical transformations catalyzed by the indicated enzymes are illustrated in bold lettering and described in the text.

L-threonine biosynthesis involves centeral metabolism including glycolysis, pentose phosphate pathway, TCA cycle and anaplerotic pathways between glycolysis and TCA cycle, prior to its terminal pathway (Fig. 14.1). 

Miyajima R, Otsuka SI, Shiio I (1968) Regulation of aspartate family amino acid biosynthesis in Brevibactenium flavunr, I. Inhibition by amino acids of the enzymes in threonine biosynthesis. JBiochem 63 139-148... 

Malumbres, M. and Martin, J.F. (1996) Molecular control mechanisms of lysine and threonine biosynthesis in amino... 

Reinscheid, D., Kircher, M., and Sahm, H. (1991) Amplification of three threonine biosynthesis genes in Corynehacterium glutamicum and its... 

Wormser and Pardee 101), in a study of the feedback mechanism of threonine biosynthesis, observed that L-threonine competitively inhibited the aspartyl phosphate reaction. They obtained a value of fiTm = 6 X 10 M for L-aspartate in the reaction and a Michaelis inhibition constant of 4 X 10 M for L-threonine. 

Aarnes, H, 1978, Regulation of threonine biosynthesis in barley seedlings (Hordeum vulgare, L.), Planta, 140 185. 

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