Amino acids production

The starting amino acid for nylon-11 is produced from methyl ricinoleate [141 -24-2] which is obtained from castor oil (qv). The methyl ricinoleate is pyrolized to methyl 10-undecylenate [25339-67-7] and heptanal [111-71-7]. The unsaturated ester is hydroly2ed and then converted to the amino acid by hydrobromination, followed by ammoniation and acidification. The CO-amino acid product is a soft paste containing water, which is dried in the first step of the polymeri2ation process. 

Refs. 21, 22, 155. Abbreviations AHV, a-amino-(3-hydroxyvaleric acid Horn, L-homoserine AEG, (3 -(2-aminoethyl)-L-cysteine ppc, phosphoenolpymvate carboxylase the strain improvement largely depends on the transduction technology sensitive resistant —, auxotroph or deficient , leaky auxotroph +, prototrophic revertant. Table 7. Amino Acid Production from Hydrocarbons ... 

Table 9. Amino Acid Production by Semifermentation Process ...

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. 

In Parenteral and Enteral Nutrition. Amino acid transfusion has been widely used since early times to maintain basic nitrogen metaboHsm when proteinaceous food caimot be eaten. It was very difficult to prepare a pyrogen-free transfusion from protein hydrolysates. Since the advances in L-amino acid production, the crystalline L-amino acids have been used and the problem of pyrogen in transfusion has been solved. The formulation of amino acid transfusion has been extensively investigated, and a solution or mixture in which the ratio between essential and nonessential amino acid is 1 1, has been widespread clinically. Special amino acid mixtures (eg, branched chain amino acids-enriched solution) have been developed for the treatment of several diseases (93). 

I. Kambe in K. Aida and co-eds.. Biotechnology of Amino Acid Production, Elsevier, Amsterdam, The Netherlands, 1966, pp. 81—89. 

P-amino acid products. Treatment of oxazoline 53 with 7V-lithiopiperidine followed by alkylation with iodomethane affords aniline derivative 54 in 94% yield and 99% de. Hydrolysis of the oxazoline group provided amino acid 55 in 92% yield and >99% ee. 

In this chapter we consider amino acid production by fermentation and by chemo-enzymatic methods. We first consider the stereochemistry of amino adds and the importance of chirality in chemical synthesis. General approaches to amino add fermentation and recovery of amino adds from fermentation broths are then dealt with, followed by a detailed consideration of the production of L-phenylalanine by direct fermentation. Later in this chapter, chemo-enzymatic methods of amino acid... 

Two appendices are included at the end of this chapter. The first is intended to serve as a reminder, for those of you who might need it, of the nomendature and representation of stereoisomers. The second appendix contains descriptions of various chemo-enzymatic methods of amino acid production. This appendix has been constructed largely from the recent primary literature and includes many new advances in the field. It is not necessary for you to consult the appendix to satisfy the learning objectives of the chapter, rather the information is provided to illustrate the extensive range of methodology assodated with chemo-enzymatic approaches to amino add production. It is therefore available for those of you who may wish to extend your knowledge in this area. Where available, data derived from die literature are used to illustrate methods and to discuss economic aspects of large-scale production. 

Figure 10.4. Effect on apatite-collagen isotopic fractionation due to inhibition of amino acid production and preferred use of exogenous amino acids. Carnivore and herbivore, both based on C3 plants, have similar bulk isotopic composition of total edible tissues (T), leading to similar 5 C for apatite carbonate (AP). Collagen (CO) of carnivore is more enriched in Cthan that of herbivore, because of preferential utilization of amino acids derived from protein (P) of herbivore flesh in construction of carnivore s proteins. C ss = assimilated carbon.

Entry Isatin Amino acid Product Yield (%) Purity (%)... 

Kineret is the tradename given to a recently approved product based on the latter strategy. Indicated in the treatment of rheumatoid arthritis, the product consists of a recombinant form of the human IL-1 receptor antagonist. The 17.3 kDa, 153 amino acid product is produced in engineered E. coli and differs from the native human molecule in that it is non-glycosylated and contains an additional N-terminal methionine residue (a consequence of its prokaryotic expression system). 

One interesting paper addresses amino acid production.37 The authors describe a fed-batch process for production of amino acids, such as L-lysine (from Corynebacterium glutamicium) and L-threonine (from Escherichia coli). For the fermentation broth of the L-lysine, the optical density, ammonium, and L-lys were measured. For L-threonine, OD, ammonium, and L-thr were measured. For all materials, the values were deemed acceptable and comparable with the reference methods. 

In an original application, Yasuda et al have used both l-AAO and d-AAO, and L-lysine oxidase to oxidize o ,Ci -diamino acids. The reactions produce the expected a-keto w-amino acid products, but these then spontaneously cyclize to form cyclic a-imino acids. These compounds are then substrates for the authors recently discovered A methyl amino acid dehydrogenase (NMAADH) from Pseudomonas putida, producing the pure L-cyclic amino acid (Scheme 5). 

Protein ALBP-PX was the first pyridoxamine-conjugated protein to be synthesized and structurally characterized. Under single-turnover conditions, this protein demonstrated amino acid production rates of only 56% of the free cofactor. However, depending on the nature of the a-keto acid, ALBP-PX did show a range of optical inductions for the amino acid product. Notably, enantiomeric excesses in the order of 94% were observed for the production of valine. Additionally, several trends were noted. All amino acid products that showed optical induction favored the 1-enantiomer, except alanine, which favored the d-enantiomer. Furthermore, a-keto acids with branched side chains... 

H. Enei u. Y. Hirose, Recent Research on the Development of Microbial Strains for Amino Acid Production, Biotcchnol. Genet. Eng. Rev. 1984, 101. 

Ureine Fragment Parent Peptide or Amino Acid Product Yield Ref... 

Presumably because of the relatively high content of phenolic amino acids, products based on milk are strongly autofluorescent when viewed after either 360 nm or 490 nm wavelength excitation. Methods for fluorescence reduction such as prior staining with Toluidine Blue O or Evan s Blue can be employed, especially on sectioned material where artifactual collapse of the emulsion which is caused by the charged nature of the dye, is not an issue [22],... 

Yield and % ee in parentheses are using the pseudoenantiomeric catalysts 7b or 7a. h%Yield to hydrolyzed amino acid product. cNo Product Obtained. tBuOiCCHjBr. 

Protected glycine derivatives have been used as the nucleophilic partner in enantioselective syntheses of amino acid derivatives by chiral PTC (Scheme 10.9). Loupy and co-workers have reported the addition of diethyl acetylaminomalonate to chalcone without solvent with enan-tioselectivity up to 82% ee [44]. The recent report from the Corey group, with catalyst 8a used in conjunction with the benzophenone imine of glycine t-butyl ester 35, discussed earlier, results in highly enantioselective reactions (91-99% ee) with various Michael acceptors (2-cyclo-hexenone, methyl acrylate, and ethyl vinyl ketone) to yield products 71-73 [21], Other Michael reactions resulting in amino acid products are noted [45]. 

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