<p>Aspartate kinase catalyzes the first step in the biosynthesis of Lys (via its precursor diaminopimelate), Met, and Thr. In <taxon tax_id="562">Escherichia coli</taxon>, a distinct isozyme is inhibited by each of these three amino acid end products [<cite idref="PUB00006443"/>]. The Met-sensitive (I) and Thr-sensitive (II) forms are bifunctional enzymes fused to homoserine dehydrogenase, which catalyses the next step in the biosynthesis of these amino acids. Inn contrast, the Lys-sensitive form (III) is a monofunctional enzyme; homoserine dehydrogenase is not part of the Lys biosynthetic pathway.</p>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> This entry represents aspartate kinase the first step of the Lysine-DAP pathway. It is a subclass of the aspartate kinases that are mostly Lys-sensitive and are not fused to homoserine dehydrogenase. The E. coli enzyme is a homodimer, while the Bacillus and Corynebacterium enzymes are alpha 2/beta 2 heterotetramers, where the beta subunit is translated from an in-phase alternative initiator at Met-246 [<cite idref="PUB00033949"/>, <cite idref="PUB00033950"/>]. The protein slr0657 from Synechocystis PCC6803 is extended by a duplication of the C-terminal region corresponding to the beta chain. Incorporation of a second copy of the C-terminal domain may be quite common in this subgroup of aspartokinases.</p> Aspartate kinase, monofunctional class