Biosynthesis of the Aspartate Family of Amino Acids

Diaminopimelate, lysine, methionine, and threonine derive most of their carbon atoms from L-aspartate, and these amino acids are therefore often referred to as the aspartate family. Their biosynthesis is effected by a complex pathway involving common intermediates from which multiple branches lead to the end products. The so-called aspartate pathway has several features that distinguish it from other pathways of amino acid biosynthesis and lend its study particular interest in the contexts of bacterial physiology and biochemical evolution. A number of different mechanisms for the control of the aspartate pathway that has evolved in the eubacteria and even within the genus Bacillus is discussed in this chapter. The primary focus of this chapter is on B. subtilis and closely related species. The aspartate pathway splits after the synthesis of aspartate semialdehyde, one branch leading to biosynthesis of diaminopimelate and lysine and the other leading to biosynthesis of threonine and methionine. The branch point enzyme homoserine dehydrogenase is the counterpart of dihydrodipicolinate synthase in controlling the utilization of aspartate semialdehyde for the biosynthesis of threonine and methionine by catalyzing the NADPH-dependent reduction of L-aspartate semialdehyde to L-homoserine. The major route for the biosynthesis of aspartate from glycolytic intermediates involves the carboxylation of pyruvate to oxaloacetate and subsequent transamination.