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>Dihydropicolinate synthase (DHDPS) is the key enzyme in lysine biosynthesis via the diaminopimelate pathway of prokaryotes, some phycomycetes and higher plants. The enzyme catalyses the condensation of L-aspartate-beta-semialdehyde and pyruvate to dihydropicolinic acid via a ping-pongmechanism in which pyruvate binds to the enzyme by forming a Schiff-basewith a lysine residue [<cite idref="PUB00003343"/>]. Three other proteins are structurally related to DHDPS and probably also act via a similar catalytic mechanism. These are <taxon tax_id="562">Escherichia coli</taxon> N-acetylneuraminate lyase (<db_xref db="EC" dbkey="4.1.3.3"/>, <db_xref db="INTERPRO" dbkey="IPR005264"/>) (gene nanA), which catalyzes the condensation of N-acetyl-D-mannosamine and pyruvate to form N-acetylneuraminate; <taxon tax_id="382">Rhizobium meliloti</taxon> (Sinorhizobium meliloti) protein mosA [<cite idref="PUB00002226"/>], which is involved in the biosynthesis of the rhizopine 3-O-methyl-scyllo-inosamine; and E. coli hypothetical protein yjhH. The sequences of DHDPS from different sources are well-conserved. Thestructure takes the form of a homotetramer, in which 2 monomers arerelated by an approximate 2-fold symmetry [<cite idref="PUB00003343"/>]. Each monomer comprises 2 domains: an 8-fold alpha-/beta-barrel, and a C-terminal alpha-helical domain. The fold resembles that of N-acetylneuraminate lyase. The activesite lysine is located in the barrel domain, and has access via 2 channelson the C-terminal side of the barrel.</p> Dihydrodipicolinate synthase, DapA