Synthesis L-phenylalanine

D- or L-phenylalanine induces the enzyme phenylalanine aminoaminotransferase, which is required for L-phenylalanine synthesis. 

The use of interm iates as substrates in L-phenylalanine synthesis avoids inhibition by metabolites. Phenylpyruvic add, an intermediate precursor in tfie biosynthesis of L-phenylalanine, can be converted to L-phenylalanine. L-aspartic add is often used as an amino donor. The amino group can only be transfdred from an... 

L-Phenylalanine aminotransferases (classified as tyrosine aminotransferase, E.C. 2.6.1.5 which also acts on phenylalanine) are enzymes useful in L-phenylalanine synthesis, as mentioned above, and have been studied in various thermophilic bacteria by Schutten et al. [185]. These workers looked at several Bacillus isolates... 

The neurotransmitter must be present in presynaptic nerve terminals and the precursors and enzymes necessary for its synthesis must be present in the neuron. For example, ACh is stored in vesicles specifically in cholinergic nerve terminals. It is synthesized from choline and acetyl-coenzyme A (acetyl-CoA) by the enzyme, choline acetyltransferase. Choline is taken up by a high affinity transporter specific to cholinergic nerve terminals. Choline uptake appears to be the rate-limiting step in ACh synthesis, and is regulated to keep pace with demands for the neurotransmitter. Dopamine [51 -61-6] (2) is synthesized from tyrosine by tyrosine hydroxylase, which converts tyrosine to L-dopa (3,4-dihydroxy-L-phenylalanine) (3), and dopa decarboxylase, which converts L-dopa to dopamine. 

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. 

Aspartame (L-aspartyl-L-phenylalanine methyl ester [22839-47-0]) is about 200 times sweeter than sucrose. The Acceptable Daily Intake (ADI) has been estabUshed by JECFA as 40 mg/kg/day. Stmcture-taste relationship of peptides has been reviewed (223). Demand for L-phenylalanine and L-aspartic acid as the raw materials for the synthesis of aspartame has been increasing, d-Alanine is one component of a sweetener "Ahtame" (224). 

Qf-receptor blocking agent, 1, 176 Phenylalanine hydroxylase in tyrosine synthesis from phenylalanine, 1, 261 L-Phenylalanine hydroxylase mechanism, 1, 261 Phenyl azide formation... 

The starting material in the following synthesis is t-butvloxycarbonyl-L-aspartyl-L-tyrosyl-L-methionylglvcyl-L-tryptophyl-L-methionvl-L-aspartvl-L-phenylalanine amide designated (SMI. 

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... 

Production of phenylalanine starts after depletion of tyrosine at about 6 hours. This is logical since the micro-oiganism needs a certain amount of tyrosine, for example to synthesise key enzymes, but synthesis of L-phenylalanine is feedback regulated if tyrosine is present. 

This discrepancy is due to die fact that other products such as formate, are formed in very small amounts as byproducts of the metabolic routes leading to L-phenylalanine and polymer synthesis. Of course, part of die glucose is also used for die metabolic activities in the micro-organism necessary to maintain the cells in a viable state, this is termed the maintenance energy requirement... 

Specific information about the optimum conditions for the synthesis and the activity of the enzyme has been reported for Pseudomonas fluorescens screening of various micro-organisms resulted in the selection of a P. fluorescens strain with an initial rate of conversion of 3 g P h 1 in an imoptimised state. The following conclusions could be made concerning the production of L-phenylalanine by P. fluorescens ... 

Auxotrophic mutant lack one or more enzymes involved in the synthesis of amino acids (such as tyrosine). This prevents accumulation of the amino acid and thus avoids feedback inhibition of enzymatic steps in the L-phenylalanine pathway. 

Cardinaux F, Howard JC, Taylor GT, Scheraga HA (1977) Block copolymers of amino-acids. 1. Synthesis and stmcture of copolymers of L-alanine or L-phenylalanine with D, L-lysine-D7 or D, L-lysine. Biopolymers 16 2005-2028... 

The same reagents can be used to form amides from carboxylic acids and amines, a method which is applicable to peptide synthesis. Condensation of A-benzyloxycarbonyl-L-phenylalanine and ethyl glycinate hydrochloride gave an 85% yield of purified dipeptide. 

Table 3.12 surveys current industrial applications of enantioselective homogeneous catalysis in fine chemicals production. Most chiral catalyst in Table 3.12 have chiral phosphine ligands (see Fig. 3.54). The DIP AMP ligand, which is used in the production of L-Dopa, one of the first chiral syntheses, possesses phosphorus chirality, (see also Section 4.5.8.1) A number of commercial processes use the BINAP ligand, which has axial chirality. The PNNP ligand, on the other hand, has its chirality centred on the a-phenethyl groups two atoms removed from the phosphorus atoms, which bind to the rhodium ion. Nevertheless, good enantio.selectivity is obtained with this catalyst in the synthesis of L-phenylalanine. 

Burke TR Jr, Smyth M, Nomizu M, Otaka A, Roller PP. Preparation of fluoro- and hydroxy-4-(phosphonomethyl)-D,L-phenylalanine suitably protected for a solid-phase synthesis of peptides containing hydrolytically stable analogues of O-phosphotyrosine. J Org Chem 1993 58 1336-1340. 

Synthesis of 1-boraadamantane adducts with ethanolamine, L-phenylalanine, L-cysteine and and L-leucine methyl esters was reported (Table 3). The structures of three of them were supported by X-ray analysis (Table 1) <2003JME2823>. 

Peptidic photoprobes can be based on the photoreactive amino acid p-benzoyl-L-phenylalanine inserted into a peptide in place of a natural aromatic residue by peptide synthesis [65] or by manipulation of the genetic code [66]. The use of p-benzoyl-L-phenylalanine for this purpose is not new, but the nature of peptide probes naturally offers opportunities for the location of linkage sites by proteomic analysis [67]. 

Stereoselective synthesis of pseudo C2-symmetrical 1,3-dibenzyldiamino alcohol (S,S) (323) a core unit of HIV protease inhibitors, and the two meso-stereoisomers (323a) and (323b) was achieved by stereocontrolled addition of benzylmagnesium chloride to nitrones (63a) and (63b) (Scheme 2.137). The yield of (S,S)-(323), based on N-Boc-L-phenylalaninal, accounts for 23% (Scheme 2.137) (211). 

J Kovacs, R Gianotti, A Kapoor. Polypeptides with known repeating sequence of amino acids. Synthesis of poly-L-glutamyl-L-alanyl-L-glutamic acid and polyglycyl-L-phenylalanine through pentachlorophenyl active ester. J Am Chem Soc 88, 2282, 1966. 

Amidocarbonylation methodology can also be applied to the synthesis of N-acclyl- (D,L)-phenylalanine, a key intermediate for aspartame (1-aspartyl-l-phenylalanine methylester), from styrene oxide (via isomerization to phenac-etaldehyde) [24] or benzyl chloride [25] in good yields. 

Synthesis of Substituted Derivatives of L-Phenylalanine and of other Non-natural L-Amino Acids Using Engineered Mutants of Phenylalanine Dehydrogenase... 

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