Hct

Aspartic -y-semialdehyde

1 Homoserine dehydrogenase Homoserine Leucine -.

Homoserine kinase

Methionine

Pyruvate

Dihydrodipicolinate synthetase

Diaminopimelate

Threonine

Figure 3. Regulation of lysine production in the metabolic pathway.

Feedback inhibition Feedback repression

Diaminopimelate have an amphoteric character, when the pH is adjusted lower than p-K^, the amino acids change from zwitterion to cationic form. When a fermentation broth with a pH adjusted lower than pKi is passed through the strong cation exchange resin, the amino acid cation being exchanged with a counterion such as H + or ammonium ion is removed continuously until the concentration on the ion exchange resin reaches a value corresponding to equilibrium with that in the fermentation broth. The adsorbed amino acids are then eluted by ammonia water or other eluant. If ammonia water is used for the eluant, the counterion form of the ion exchange resin changes to the ammonium form simultaneously, and no generation process is necessary; moreover, almost no inorganic substances are contained in elution with the amino acid. The elution is condensed until the somewhat higher saturated concentration of amino acids is evaporated and crystallized to obtain amino acid crystals.

The crystallization method for an amino acid is selected on the basis of the characteristics of the amino acid and the degree of impurity contained in solution. The solubility minimum at the isoelectric point is useful for crystallizing amino acids. L-Aspartic acid and L-tyrosine, which show comparatively lower solubility, for example, are first dissolved in alkali or acid solution and then crystallized by neutralization to pi. On the other hand, L-lysine hydrochloride and L-glutamate, which show higher solubility, crystallize by the condensed crystallization method.

L-Leucine, L-isoleucine, and L-valine, branched-chain amino acids from which higher purity crystals are difficult to obtain, react with benzoic sulfonic acid derivatives to form corresponding complexes.

For pharmaceutical use, it is critical to prevent contamination by pyrogen substances and microorganisms. Pyrogen is a toxin consisting of polysaccharides and protein. It is excreted mainly by Gram-negative bacilli, and it is highly hydrophobic. The pyrogens are effectively adsorbed on activated carbon. Sterilization by heating and ultrafiltration membranes (molecular weight cutoff, 10,000 to 100,000) are used as well for rejection of pyrogens and microorganisms.

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