Early History of the Breeding of Amino Acid-Producing Strains

Amino acid production started in Japan in 1908 with the extraction of monosodium glutamate (MSG) from acid hydrolysates of proteins. In addition to extraction, other methods of amino acid production include chemical synthesis, fermentation, and enzymatic synthesis both for glutamic acid and other amino acids. In this chapter, we review the historical transition of these production methods; currently, fermentation is the chief production method of amino acids. All wild-type microorganisms possess a negative feedback control system (feedback inhibition and repression) on the enzymes within the amino acid biosynthetic pathways. Therefore, techniques for the development of amino acid-overproducing strains and also for the establishment of enzymatic processes for the synthesis of amino acids were developed to artificially release these feedback controls. The key techniques used to bypass these controls are as follows: (a) artificial acceleration of the easy efflux of intracellularly synthesized amino acids outside of cells; (b) limitation of the concentration level of feedback inhibitors (amino acids) using auxotrophic mutants; (c) genetic desensitization of key enzymes to feedback inhibition by mutation and selection of amino acid analog-resistant mutants; (d) amplification of genes coding for desensitized biosynthetic enzymes; (e) disruption of amino acid degradation activity; and (f) application of enzyme reactions free from feedback controls for amino acid synthesis. Selection and breeding of amino acid producers by the application of these techniques is described.