Production of amino acids:: Physiological and genetic approaches

Large scale fermentative production Of L-amino acids is still an important goal of modern biotechnology. Very large amounts Of L-glutamate and L-lysine, as well as significant quantities Of L-threonine and L-phenylalanine and other amino acids for the application in food, feed, and for pharmaceutical purposes are currently produced by fermentation using mainly the two organisms Corynebacterium glutamicum and Escherichia coli. In the past 50 years, development of producing strains initially depended mostly on classical strain breeding involving repeated random mutation and selection. The development of modern tools of molecular biology enabled more rational approaches to strain improvement. The purposeful design of metabolic pathways, transport functions, and regulatory mechanisms in order to increase the yield and productivity of amino acid producing strains is based on the knowledge of fundamental aspects of physiology, biochemistry, molecular biology, and bioprocess engineering of the relevant organisms in general and of specific producing strains in particular. In addition to genome sequencing, modern techniques of transcriptome, proteome, metabolome, and metabolic flux analysis have recently been introduced in order to identify new and important target genes and to quantify metabolic activities. The fundamental physiological and biochemical principles relevant for amino acid production as well as modern developments in the direction of a purposeful metabolic design will be summarized.