<p>Bacteria, plants and fungi metabolise aspartic acid to produce four amino acids - lysine, threonine, methionine and isoleucine - in a series of reactions known as the aspartate pathway. Additionally, several important metabolic intermediates are produced by these reactions, such as diaminopimelic acid, an essential component of bacterial cell wall biosynthesis, and dipicolinic acid, which is involved in sporulation in Gram-positive bacteria. Members of the animal kingdom do not posses this pathway and must therefore acquire these essential amino acids through their diet. Research into improving the metabolic flux through this pathway has the potential to increase the yield of the essential amino acids in important crops, thus improving their nutritional value. Additionally, since the enzymes are not present in animals, inhibitors of them are promising targets for the development of novel antibiotics and herbicides. For more information see [<cite idref="PUB00034672"/>].</p><p>Aspartate-semialdehyde dehydrogenase, the second enzyme in the aspartate pathway, converts aspartyl phosphate to aspartate-semialdehyde, the branch point intermediate between the lysine and threonine/methionine pathways. Based on sequence alignments, the aspartate-semialdehyde dehydrogenase family appears to have two distinct subgroups, one found in most bacteria (Gram-positve and Gram-negative), while the other is found primarily in organisms lacking peptidoglycan (archaea,fungi and some bacteria). Most studies have been performed on enzymes isolated from Gram-negative bacteria [<cite idref="PUB00034673"/>, <cite idref="PUB00029242"/>, <cite idref="PUB00029661"/>, <cite idref="PUB00034674"/>]. The N-terminal domain forms the active site and NADP-binding pocket, while C-terminal domain is primarily involved in hydrophobic intersubunit contacts. The catalytic mechanism involves the formation of a covalent thioester acyl-enzyme intermediate mediated through nucleophilic attack by an active site cysteine residue on the substrate aspartyl phosphate. Release of inorganic phosphate is followed by hydride transfer from NADPH to yield the product. The recently described archaeal structure suggests that the two subgroups of aspartate semi-aldehyde dehydrogenase share similar structures and have an identical catalytic mechanism, despite their relatively low sequence identity [<cite idref="PUB00034675"/>]. Unlike the bacterial enzymes, the archaeal enzyme utilised both NAD and NADP as cofactor.</p><p>This entry represents both branches of the asparate-semialdehyde dehydrogenase family.</p>