Aspartate p-semialdehyde

Enzyme assisted aldol condensation was the key step of the synthesis of 3-deoxy-D-ara mo-heptulosonic acid 7-phosphate (Scheme 63) [154], In the four steps synthesis of DAHP Whitesides started from A-acetyl -D/L-aspartate P-semialdehyde and dihydroxyacetone phosphate. The required threo stereochemistry was generated by using commercial rabbit muscle aldolase as catalyst. 

Mosf of the chemistry has been considered already. The reduction of aspartate via p-aspartyl phosphate and aspartate p-semialdehyde ° is a standard one. Conversion to methionine can occur in two ways. In E. coU homoserine is succinylated with succinyl-CoA. The y-succinyl group is then replaced by the cysteine molecule in a PLP-dependent y-replacement reaction (Fig. 24-13). The product cystathionine (Eq. 14-33) undergoes elimination to form homocysteine. A similar pathway via 0-phospho-homoserine occurs in chloroplasts of green plants. ... 

Regulation of lysine biosynthesis. ASA, aspartate-p-semialdehyde DHDP, dihydrodipicolinate DAP, a, e-diaminopimelate and Hse, homoserine. (1) Aspartate kinase,... 

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). 

Aldol condensation of pyruvate and L-aspartate - /3-semialdehyde Phosphomonoesters hydrolysis (p-nitrophenyl phosphate, 3.3 x 10 )... 

Pyruvate/PEP oxaloacetate aspartate p-alanine malonate semialdehyde 3HP 1/0 -32.3 US7186541 B2 Cargill [27]... 

Zhang, W.W. Jiang, W.H. Zhao, G.P. Yang, Y.L. Chiao, J.S. Expression in Escherichia coli, purification and kinetic analysis of the aspartokinase and aspartate semialdehyde dehydrogenase from the rifamycin SV-producing Amycolatopsis mediterranei U32. Appl. Microbiol. Biotechnol., 54, 52-58 (2000)... 

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. 

In plants and microorganisms, l-T. is biosynthesized from phosphohomoserine by a y-elimination of phosphate followed by P-replacement with an OH-group. Hiis total reaction is catalysed by the pytidoxal phosphate enzyme, l-T. synthase (EC 4.2.99.2). Hie phosphohomoserine is derived from aspartate via as-partyl phosphate, aspartate semialdehyde and homoserine. 

So, the biosynthesis of methionine (Met, M), the first of the essential amino adds to be considered (Scheme 12.13), begins by the conversion of aspartate (Asp, D) to aspartate semialdehyde in the same way glutamate (Glu, E) was converted to glutamate semialdehyde (vide supra. Scheme 12.6). Phosphorylation on the terminal carboxylate of aspartate (Asp, D) by ATP in the presence of aspartate kinase (EC 2.7.2.4) and subsequent reduction of the aspart-4 yl phosphate by NADPH in the presence of aspartate semialdehyde dehydrogenase (EC 1.2.1.11) yields the aspartate semialdehyde. The aspartate semialdehyde is further reduced to homoserine (homoserine oxoreductase, EC 1.1.1.3) and the latter is succinylated by succinyl-CoA with the liberation of coenzyme A (CoA-SH) in the presence of homoserine O-succinyl-transferase (EC 2.3.1.46). Then, reaction with cysteine (Cys, C) in the presence of cystathionine y-synthase (EC 2.5.1.48) produces cystathionine and succinate. In the presence of the pyridoxal phosphate protein cystathionine P-lyase (EC 4.4.1.8), both ammonia and pyruvate are lost from cystathionine and homocysteine is produced. Finally, methylation on sulfur to generate methionine (Met, M) occurs by the donation of the methyl from 5-methyltetrahydrofolate in the presence of methonine synthase (EC 2.1.1.13). 

Fig. 24.26. Regulation in lysine biosynthesis in Brevibacterium flavum and Corynebacterium glutamicum. (ASA aspartate semialdehyde DHDP dihydrodipicolinate Hse hemoserine DAP diaminopimelate.) (Microbial Technology, 2nd ed., VoL 1, p. 220, Academic Press, New York, 1979.)...

---