A,e-Diaminopimelic acid

With the exception of some constituents such as high concentrations of calcium, dipicolinic aci d, and in Bacillus sphaericus, a, E-diaminopimelic acid, spore are similar to the vegetative cells in composition. 

In many organisms the immediate biosynthetic precursor of L-lysine is a,e-diaminopimelic acid (structure below). What type of enzyme would catalyze this reaction what coenzyme would be required and what type of enzyme-substrate complex would be formed ... 

Delipidated bacterial residues of human, bovine, avian, and saprophyte strains were active this can be explained by the fact that these residues contain, essentially, cell walls. It is known that mycobacterial cell-walls are mainly composed of three amino acids (alanine, glutamic acid, and a,e-diaminopimelic acid) linked to a polysaccharide containing arabinose, mannose, galactose, and muramic acid, -i and thus have an over-all composition very similar to that of the water-soluble part of the wax D of human strains. 

There appear to be two pathways for the biosynthesis of lysine among microorganisms. In E. coli there is strong evidence that the diamino dicarboxylic acid, a,e-diaminopimelic acid, is a precursor of lysine. Diaminopimelic acid has been isolated from bacteria - and found to be decarboxylated by a specific decarboxylase occurring in wild-type E. coli. This enzyme has been found to be constitutive rather than adaptive, and it is absent from certain of the lysine auxotrophs. "... 

D,L-a,e-diaminopimelic acid No Rf values Methanol-water-5N HCI pyridine. 80 17.5 2.5 10 Paper No. 1, Whatman, USA Visualization ninhydrin 64 1955 ... 

When the biosynthetic pathways given above are examined, it is apparent that several intermediates are indeed nonprotein ct-amino acids. Ornithine, homoserine, homocysteine, and ct-e-diaminopimelic acid are a few examples. This shows that some nonprotein amino acids originate as intermediates during the biosynthesis of... 

FIGURE 22-15 Biosynthesis of six essential amino acids from oxalo-acetate and pyruvate in bacteria methionine, threonine, lysine, isoleucine, valine, and leucine. Here, and in other multistep pathways, the enzymes are listed in the key. Note that L,L-a,e-diaminopimelate, the product of step (HI), is symmetric. The carbons derived from pyruvate (and the amino group derived from glutamate) are not traced beyond this point, because subsequent reactions may place them at either end of the lysine molecule. 

Nevertheless, an exception to the general rule of retention has recently been discovered in the form of mcfo-a,e-diaminopimelate decarboxylase from Bacillus sphaerkus (259). This PLP-dependent enzyme, which catalyzes the final step in lysine biosynthesis, is the only known amino acid decarboxylase to operate on an a-carbon having the D-configuiation (264). Inversion of configuration was demonstrated for the enzyme from Bacillus sphaerkus by conducting the decarboxylation reaction in H20 solvent and isolating as product (6I7)-l-[6-2H]lysine [Eq. (50)] ... 

The stereochemistry of meso-a,e-diaminopimelate decarboxylase from a eukaryotic source (wheat germ) also involves inversion of configuration (260). As suggested by Floss and Vederas inversion might be comprehensible if the enzyme evolved from a preexisting L-amino acid decarboxylase in which the dispositions... 

The enzyme a,E-diaminopimelate decarboxylase (EC 4.1.1.20) decar-boxylates the (R) center of (25,6/ )-ffieso-diaminopimelic acid 262 to give lysine 257a (Scheme 69). When this reaction was conducted in and... 

Most common amino acids have been given full or part sections in this review and less common amino acids (e.g., a,m-diaminopimelic acid 262) have been discussed where appropriate. However, two less common amino acids have been left to this section mainly because of the lack of opportunity to discuss them in one of the other sections of this chapter. 

The fermentation process to produce lysine was first developed by Pfizer. Escherichia coli synthesized its own lysine requirements by converting carbohydrate and ammonia to a,s-diaminopimelic acid (DAP). Its decarboxylation resulted in lysine. The industrial fermentation employed an E, coli mutant devoid of DAP-decarboxylase. It accumulated substantial DAP in the culture medium. After maximum DAP yields were attained, a second organism, another E. coli strain or Aerobacter aerogenis, was used as a source of DAP-decarboxylase to produce lysine. This second organism was devoid of lysine decarboxylase. Lysine, thus, accumulated in the broth. The reactions are shown in Fig. 24.25. 

The overall fold of MIPS is similar to that of diaminopimelic acid dehydrogenase from Corynebacterium glutamicum and dihydrodipicolinate reductase from E. coli. Though the reactions catalyzed by these enzymes are quite different, they all use either NAD+ or NADP+ bound to a structurally similar Rossmann fold domain, and all three contain a (3 sheet domain located underneath the Rossmann fold and directly beneath the nicotinamide moiety that defines part of the active site (Norman et al., 2002 Stein and Geiger, 2002). 

Diethyl a, -dibromopimelate refluxed 15 hrs. with activated Na-azide in abs. ethanol, the crude product dissolved in abs. benzene, treated dropwise with a soln. of triphenylphosphine in benzene, refluxed 5 hrs., the solvent removed in vacuo, and the residue refluxed 5 hrs. with a 1 1 mixture of 40%-HBr and acetic acid -> a, -diaminopimelic acid. Y ca. 100%. F. e. s. F. Lingens, Z. Naturf. 15b, 811 (1960). 

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