The Threonine-Synthesis Pathway In Escherichia coli

Threonine is an essential amino acid for birds and mammals. Since it can't be synthesised in vivo and must therefore be acquired through the diet, there is a considerable interest in its economic industrial production. The five-step metabolic pathway for threonine synthesis from aspartate in the bacterium Escherichia coli (E. coli) has been well characterised. The kinetics of all the five pathway enzymes from E. coli have previously been studied extensively, however, this information has not been applied to producing a global theoretical model of the pathway under conditions in vivo. Not only have experimental temperatures and pH levels been well outside the physiological range, but also many studies have not considered the effects of end-product inhibition, negative feedback control or reversible reactions.

In 2001, Christophe Chassagnole, Badr Rais, Eric Quentin, David A. Fell and Jean-Pierre Mazat published a kinetic model describing the threonine-synthesis pathway in E. coli (see Figure 1 below). Their aim was to summarise the kinetic behaviour of each enzyme in a single equation. This equation accounts for the effect of the products as competitive inhibitors of the substrates in the forward reaction and where applicable, as substrates of the reverse reactions. Co-operative feedback inhibition by threonine and lysine was also included. Each individual rate equation was then incorporated into a complete theoretical model of the threonine pathway. This model is able to predict the behaviour of the pathway under natural or engineered conditions.

The complete original paper reference is cited below:

An integrated study of threonine-pathway enzyme kinetics in Escherichia coli, Christophe Chassagnole, Badr Rais, Eric Quentin, David A. Fell and Jean-Pierre Mazat, 2001, Biochemical Journal, 356, 415-423. (The PDF and full text versions of the article are available on the Biochemical Journal website.) PubMed ID: 11368768

The raw CellML description of the model can be downloaded in various formats as described in the section “Download This Model”.

Figure 1. Threonine-synthesis pathway from aspartate in E. coli. The different steps are catalysed by aspartate kinases I and III (AK I and AK III), aspartate semialdehyde dehydrogenase (ASD), homoserine dehydrogenase (HDH), homoserine kinase (HK) and threonine synthase (TS). The abbreviations used are: asp, aspartate; aspp, beta-aspartyl phosphate; ASA, aspartic beta-semialdehyde; hs, homoserine; hsp, O-phospho-homoserine; thr, threonine and lys, lysine. Solid black lines represent the individual reaction steps of the pathway and the dashed red lines represent reaction inhibition by threonine and lysine.