Amino acids manufacture

Enzymatic hydrolysis of A/-acylamino acids by amino acylase and amino acid esters by Hpase or carboxy esterase (70) is one kind of kinetic resolution. Kinetic resolution is found in chemical synthesis such as by epoxidation of racemic allyl alcohol and asymmetric hydrogenation (71). New routes for amino acid manufacturing are anticipated. 

Microbial Pathway Engineering for Amino Acid Manufacture... 

Regarding the economical viability of the plant, the retention and stability of acylase are essential features for the process. An ultrafiltration unit retains acylase as the mobile catalyst in the reactor. Alternatively, acylase can be immobilized in a fixed or fluidized bed. A mobile catalyst system is preferred compared to the immobilized form, as the mobile catalyst system avoids mass-transfer limitations. Additionally, regeneration of the catalyst and scale-up of the reactor are much easier as compared to the process with the immobilized acylase. With respect to the deactivation of the catalyst, the thermal as well as the operational stability of acylase has been evaluated extensively [128, 129]. At a pH of 7, acylase appears to be sufficiently stable for L-amino acid manufacture. 

As Table 4.4 shows, there have only been 18 agricultural applications of r-DNA technology which have used MAFF s guidelines. Of these, three are amino acid manufacturing processes using E. coli and one is for production of interferon from silkworms for use as a veterinary drug. 

These techniques, in which mutant strains are selected for their ability to overproduce metabolites, represent an important advance in the industrial development of microbial synthesis. Their use to improve amino-acid manufacture was not new they had already been used to improve the titres of antibiotics but the nature of the changes introduced into the metabolism of the mutated organisms could not be interpreted in the way that was possible for amino-acid synthesis. What is, perhaps, also apparent is that the technique of interfering with the metabolic pathway between aspartate and lysine is, in principle, no different from the use of sulphite to inhibit the synthesis of ethanol (section 6.2.1.2). In one case C. glutamicum overproduces lysine, while in the other S. cerevisiae will produce glycerol. 

The procedures, described by Stoddard and Dunn (759) are convenient, rapid and quite reliable for all amino acids examined except the special cases noted. These tests, employed routinely hy Amino Acid Manufacturers since 1935, have been found to be useful preliminary criteria of purity of amino acids. The qualitative tests found to be satisfactory are indicated by - - signs in Table III. Unsatisfactory tests are indicated by — signs. Tests not performed are indicated by. . signs. 

H2N-CH2 [CH2j3.CH(NH2) COOH. Colourless needles, m.p. 224 C (decomp.), very soluble in water, insoluble in alcohol. L-(-H)-Lysine is one of the basic amino-acids occurring in particularly large quantities in the protamine and histone classes of proteins. It is an essential amino-acid, which cannot be synthesized by the body and must be present in the food for proper growth. It can be manufactured by various fermentation processes or by synthesis. 

Because of the simplicity of swiae and poultry feeds, most feed manufacturers add vitamins (qv) and trace minerals to ensure an adequate supply of essential nutrients. Amino acids (qv) such as methionine [7005-18-7] lysiae [56-87-17, threonine [36676-50-3] and tryptophan [6912-86-3], produced by chemical synthesis or by fermentation (qv), are used to fortify swiae and poultry diets. The use of these supplements to provide the essential amino acids permits diets with lower total cmde proteia coateat. 

T. E. Stewart, M Survey of the Chemistry of Amino Acids-Reducing Sugar Reaction in Relation to Aroma Production, Scientific and Technical Surveys No. 61, British Eood Manufacturing Industries Research Association, London, Dec. 1969. 

Pharmaceuticals. -Hydroxybenzaldehyde is often a convenient intermediate in the manufacture of pharmaceuticals (qv). For example, 2-(p-hydroxyphenyl)glycine can be prepared in a two-step synthesis starting with -hydroxybenzaldehyde (86). This amino acid is an important commercial intermediate in the preparation of the semisynthetic penicillin, amoxicillin (see ANTIBIOTICS, P-LACTAMs). Many cephalosporin-type antibiotics can be made by this route as well (87). The antiemetic trimethobenzamide [138-56-7] is convenientiy prepared from -hydroxybenzaldehyde (88) (see Gastrointestinal agents). 

Enzymatic hydrolysis is also used for the preparation of L-amino acids. Racemic D- and L-amino acids and their acyl-derivatives obtained chemically can be resolved enzymatically to yield their natural L-forms. Aminoacylases such as that from Pispergillus OTj e specifically hydrolyze L-enantiomers of acyl-DL-amino acids. The resulting L-amino acid can be separated readily from the unchanged acyl-D form which is racemized and subjected to further hydrolysis. Several L-amino acids, eg, methionine [63-68-3], phenylalanine [63-91-2], tryptophan [73-22-3], and valine [72-18-4] have been manufactured by this process in Japan and production costs have been reduced by 40% through the appHcation of immobilized cell technology (75). Cyclohexane chloride, which is a by-product in nylon manufacture, is chemically converted to DL-amino-S-caprolactam [105-60-2] (23) which is resolved and/or racemized to (24)... 

Other L-amino acids are manufactured much more economically ia thousands of tons per year ia Japan by simplified fermentations direcdy from glucose, ethanol, acetic acid, glycerol, or / -paraffin, by means of selected auxotrophic, regulatory, and analogue-resistant bacterial mutants (94,95). 

Without other alternatives, the carboxyalkyl radicals couple to form dibasic acids HOOC(CH)2 COOH. In addition, the carboxyalkyl radical can be used for other desired radical reactions, eg, hydrogen abstraction, vinyl monomer polymerization, addition of carbon monoxide, etc. The reactions of this radical with chloride and cyanide ions are used to produce amino acids and lactams employed in the manufacture of polyamides, eg, nylon. 

Asymmetric synthesis is a method for direct synthesis of optically active amino acids and finding efficient catalysts is a great target for researchers. Many exceUent reviews have been pubHshed (72). Asymmetric syntheses are classified as either enantioselective or diastereoselective reactions. Asymmetric hydrogenation has been appHed for practical manufacturing of l-DOPA and t-phenylalanine, but conventional methods have not been exceeded because of the short life of catalysts. An example of an enantio selective reaction, asymmetric hydrogenation of a-acetamidoacryHc acid derivatives, eg, Z-2-acetamidocinnamic acid [55065-02-6] (6), is shown below and in Table 4 (73). 

An estimation of the amount of amino acid production and the production methods are shown ia Table 11. About 340,000 t/yr of L-glutamic acid, principally as its monosodium salt, are manufactured ia the world, about 85% ia the Asian area. The demand for DL-methionine and L-lysiae as feed supplements varies considerably depending on such factors as the soybean harvest ia the United States and the anchovy catch ia Pern. Because of the actions of D-amiao acid oxidase and i.-amino acid transamiaase ia the animal body (156), the D-form of methionine is as equally nutritive as the L-form, so that DL-methionine which is iaexpensively produced by chemical synthesis is primarily used as a feed supplement. In the United States the methionine hydroxy analogue is partially used ia place of methionine. The consumption of L-lysiae has iacreased ia recent years. The world consumption tripled from 35,000 t ia 1982 to 100,000 t ia 1987 (214). Current world consumption of L-tryptophan and i.-threonine are several tens to hundreds of tons. The demand for L-phenylalanine as the raw material for the synthesis of aspartame has been increasing markedly. 

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