Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways [<cite idref="PUB00055043"/>].<p>There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different [<cite idref="PUB00055043"/>].</p><ul><li>The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria. </li><li>The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified. </li><li>The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana. </li><li>The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum. </li></ul><p>Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.</p><p>Dihydrodipicolinate reductase is an enzyme found in bacteria and higher plants which is involved in the biosynthesis of diaminopimelic acid, a component of bacterial cell walls, and the essential amino acid L-lysine. It catalyses the the reduced pyridine nucleotide-dependent reduction of the alpha,beta-unsaturated cyclic imine, dihydrodipicolinate, to generate tetrahydrodipicolinate as shown below [<cite idref="PUB00028085"/>]:<reaction>2,3-dihydrodipicolinate + NAD(P)H = 2,3,4,5-tetrahydrodipicolinate + NAD(P)(+)</reaction>As this enzyme is not found in mammals it is a potential target for the development of novel antibacterial and herbicidal compounds.</p><p>The structures of the <taxon tax_id="562">Escherichia coli</taxon> (<db_xref db="SWISSPROT" dbkey="P04036"/>) and <taxon tax_id="1773">Mycobacterium tuberculosis</taxon> (<db_xref db="SWISSPROT" dbkey="P72024"/>) enzymes have been determined [<cite idref="PUB00000417"/>, <cite idref="PUB00023845"/>]. The enzyme is a homotetramer where each monomer is composed of two domains, an N-terminal NAD(P)H-binding domain which forms a Rossman fold, and a C-terminal substrate-binding domain that forms an open, mixed alpha-beta sandwich.Tetramerisation occurs exclusively through interactions between C-terminal domain residues. Both enzymes show relatively little preference for either NADH or NADPH as cofactor. Conformational changes upon substrate binding bring the cofactor and substrate into close proximity and allow catalysis to occur.</p>