Aromatic Amino Acids

Abstract

Biosynthesis of the three aromatic amino acids (l-phenylalanine, l-tryptophan, l-tyrosine) and its regulation in Escherichia coli and corynebacteria are reviewed. The common aromatic biosynthetic pathway (shikimate pathway) starts with the condensation of phosphoenolpyruvate and erythrose 4-phosphate. Through six biosynthetic steps the pathway proceeds via shikimate to chorismate, from which the terminal pathways to tryptophan, phenylalanine and tyrosine branch. The first step in the common pathway is performed in E. coli by three isoenzymes, which are specifically feedback-inhibited by the three terminal products. The pathway to tryptophan starts with anthranilate formation and includes reactions with l-serine and 5-phosphoribosyl-pyrophosphate. Phenylalanine and tyrosine biosyntheses proceed via prephenate, and each include a decarboxylation and transamination step. The first committed steps of each terminal pathway are strictly regulated by feedback inhibition, repression and partly through attenuation (in E. coli). l-Tryptophan and l-phenylalanine are essential amino acids for man and most livestock. Main microbial producer strains are E. coli and Corynebacterium glutamicum. Strain development includes alleviation of the various regulatory levels (feedback inhibition resistance, derepression), both in the common aromatic pathway and in the terminal pathways. In recent years, metabolic engineering has also taken into account the fact that precursor supply may become limiting once the other impediments for carbon flux are gone. Strains with improved phosphoenolpyruvate and/or erythrose 4-phosphate supply have successfully been developed. Applications for l-tryptophan are the feed and pharmaceutical markets, while l-phenylalanine is mainly used as building block for the artificial sweetener, aspartame®. A possible application for l-tyrosine is as a building block for the synthesis of l-DOPA.