L-Aspartate semialdehyde

FIGURE 3.4 The common pathway of the aspartate-derived amino acids in Corynebacteria. The mnemonic of the genes involved are shown in parentheses below the enzymes responsible for each step. Dotted lines indicate multiple enzymatic steps, and 16 is L-aspartic acid, 17 is L-aspartyl phosphate, 18 is L-aspartate semialdehyde, 19 is L-lysine, 20 is L-homoserine, 21 is L-isoleucine, 22 is L-threonine, and 23 is L-methionine. 

Shames, S.L. Wedler, RC. Homoserine kinase of Escherichia coli kinetic mechanism and inhibition by L-aspartate semialdehyde. Arch. Biochem. Biophys., 235, 359-370 (1984)... 

L-aspartate semialdehyde <4> (<4>, mixed inhibition versus L-homoserine and ATP [4]) [4]... 

L-Homoserine is formed by a second reduction reaction, in which L-aspartic semialdehyde and DPNH participate (IV). This reaction has... 

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)... 

Figure 2 NAD biosynthesis subsystem diagram. Major functional roles are shown by 4-6 letter abbreviations (explained in Table 1) over the colored background reflecting the key aspects or modules (pathways) that comprise NAD biosynthesis in various species. Catalyzed reactions are shown by solid straight arrows, and corresponding intermediate metabolites are shown as abbreviations within ovals Asp, L-aspartate lA, Iminoaspartate Qa, quinolinic acid Nm, nicotinamide Na, nicotinic acid NaMN, nicotinic acid mononucleotide NMN, nicotinamide mononucleotide RNm, N-ribosyInicotinamide NaAD, nicotinate adenine dinucleotide NAD, nicotinamide adenine dinucleotide NADP, NAD-phosphate Trp, tryptophan FKyn, N-formylkynurenine Kyn, kynurenine HKyn, 3-hydroxykynurenine HAnt, 3-hydroxyanthranilate and ACMS, a-amino-/3-carboxymuconic semialdehyde. Unspecified reactions (including spontaneous transformation and transport) are shown by dashed arrows.

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. 

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

Fig. 10. Schematic representation of the split biosynthetic pathway of L-lysine in wildtype Corynebacterium glutamicum including the branch point of aspartate semialdehyde distribution. The metabolites derived from the aldehyde via the synthase activity are D,L-di-aminopimelate and L-lysine, whereas that resulting from dehydrogenase activity are L-threo-nine, L-methionine, and L-isoleucine. The activity of the dehydrogenase is inhibited at elevated L-threonine concentrations and its synthesis is repressed by L-methionine. Accumulating intracellular lysine causes feedback inhibition of aspartate kinase and activates lysE transcription...

A further flux control step within L-lysine synthesis is the aspartate semialdehyde branch point. The aldehyde is either used as a substrate for the homoserine dehydrogenase, or together with pyruvate as a substrate for the dihydrodipicolinate synthase (Fig. 10). Whereas the homoserine dehydrogenase is allosterically controlled in its catalytic activity by the L-threonine concentration... 

Seven enzyme catalyzed reactions are required for the synthesis of lysine from pyruvate and aspartate semialdehyde as illustrated in Fig. 3. However, enzymes catalyzing only the first and last of these reactions have been isolated from plants. Dihydropicolinate synthase facilitates the condensation of the precursors during a reaction which presumably proceeds in two steps. A double bond between the C-4 of the semialdehyde and the methyl carbon of pyruvate would be formed, with the loss of water, followed by spontaneous ring closure and the loss of a second molecule of water. Catalysis of this reaction in plant extracts was first demonstrated by Cheshire and Miflin (1975) using maize seedlings as the source of the enzyme. Mazelis et al. (1977) detected the enzyme in extracts obtained from six different taxonomic families of plants and partially purified the enzyme from wheat germ. Only the L isomer of aspartate semialdehyde was active as a substrate of this enzyme and strong cooperativity was noted when the concentration of pyruvate was varied. A dihydropicolinate synthase has also been isolated from carrot cells (Matthews and Widholm, 1978). 

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. 

L-Threonine is synthesized from L-aspartic acid via L-aspartic acid-4-phosphate and L-aspartic-jS-semialdehyde (Fig. 203). The latter is a precursor of L-lysine (D 18) as well as of L-homoserine (D 12). L-Threonine is formed from L-homoserine by synthesis of the 4-phosphate and shift to the hydroxyl group by a pyridoxal-phosphate-dependent enzyme. 

Starting from the building block of L-aspartate, the biosynthesis of L-threonine comprises five successive reactions sequencially catalyzed by aspartate kinase, aspartyl semialdehyde dehydrogenase, homoserine dehydrogenase, homoserine kinase and threonine synthase. 

A specific incorporation of [l- C,4- H]methionine [as (213)] into azetidine-2-carboxylic acid (212) without change in isotope ratio showed that the oxidation level at C-4 was unaffected in the biotransformation of (213) into (212), thus excluding as intermediates aspartic-i5-semialdehyde (214) and aspartic acid (215). °" Conflicting evidence on the relative levels of incorporation of homoserine (216) and methionine has been obtained (but the differences are quite small). However, when a relatively large amount of inactive homoserine was fed together... 

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