Lysine biosynthesis

Valine, leucine, and isoleucine biosynthesis Lysine biosynthesis Lysine degradation Arginine and proline metabolism Histidine metabolism Tyrosine metabolism Phenylalanine metabolism Tryptophan metabolism Phenylalanine, tyrosine, and tryptophan biosynthesis Urea cycle and metabolism of amino groups... 

Fig. 6. The metabolic pathway for lysine biosynthesis in Escherichia coli, which contains a missing enzyme that is not found in the genome.

Nomura et al. (1987a) attempted to minimize product inhibitory effect on the aspartate kinase step in lysine biosynthesis and enhance L-lysine production from Brevibacterium Jlavum QL-5 using a combined ED-F system. However, lysine production was not statistically different from that obtained in diffusion dialysis fermentation and about 20% greater than that achieved during conventional fermentation, thus making practically ineffective such a use of ED. 

Fig. 5. Carbon transitions in the split pathway of lysine biosynthesis in Corynebacterium glutamicum. Not all the reaction steps or all the metabolites are shown. A1 A2, A3, and A4 refer to the carbon atoms C1-C4 of aspartate and Pl5 P2, and P3 refer to Cl-C3 of pyruvate...

Lysine Glucose Flux profiling in response to feedback deregulation of lysine biosynthesis [115]... 

Diaminopimelate decarboxylase catalyzes the final step in lysine biosynthesis in bacteria. The epimerase catalyzes the interconversion of the ll- and meso isomers of diaminopimelate. Because these enzymes are absent in mammals, they are considered to be potential targets for antimicrobial agents. 

Fig. 1. Regulation of lysine biosynthesis. ASA, aspartate-/3-semialdehyde DDP, dihydro-dipicolinate DAP, a, -diaminopimelate Hse, homoserine...

Fig. 10.2 Regulation of lysine biosynthesis by feedback inhibition. The explanatory notes 1-6 within the iUnstration are intended to be read in the order of the numbers...

Most prokaryotes employ dedicated PPTs active toward specific apoprotein substrates. Fungi also utilize separate PPTs for modification of the ACPs associated with the cytosolic and mitochondrial FAS systems, as well as the a-aminoadipate reductase involved in lysine biosynthesis [8]. The former is unusual in that it is a constituent domain of the multifunctional a-subunit (Fig. 4). Surprisingly, animals appear to employ a single PPT for servicing three different apoproteins the ACP domain of the cytosolic FAS, the ACP component of the mitochondrial FAS, and the a-aminoadipate semialdehyde dehydrogenase involved in lysine catabolism. The human PPT has recently been identified and characterized (S. Smith, 2003) and its crystal structure determined in complex with Mg, CoA, and the ACP domain of the cytosolic FAS (Structural Genomics Consortium). The ACP domain is comprised of a four-helix bundle, as are the ACPs associated with type II systems. The conserved serine residue that is the site of posttranslational modification lies at the N-terminal end of helix-2 (Fig. 6B), closely juxtaposed with the pyrophosphate of CoA that is cleaved during the phosphopantetheine transfer. Helix-2 makes multiple... 

CPs are integral components of various primary and secondary metabolic pathways, including fatty acid synthesis (FAS), nonribosomal peptide synthesis (NRPS), polyketide synthesis (PKS), and lysine biosynthesis. All CPs harbor... 

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)] ... 

Bacteria synthesize lysine through one of three different pathways that are not present in mammals. " An intermediate in these pathways, wj ro-diaminopimelic acid (mDAP), is also an essential component of the bacterial cell wall. " " Consequently, the enzymes in these pathways are targets for the development of antibiotics for treatment of Gram-negative and Gram-positive bacterial infections. The enzyme DapE catalyzes the hydrolysis of N-succinyl-L,L-diaminopimelic acid to form L,L-diaminopimelic acid and succinate in the succinylase pathway of lysine biosynthesis (Figure 6(i)). 

Two distinct pathways of lysine biosynthesis have been established in bacteria and fungi. One, originating with 2-oxoglutarate and acetyl-CoA,... 

Fig. 3. Lysine biosynthesis. The successive chemical transformations catalyzed by the indicated enzymes are illustrated in bold lettering and described in the text.

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