Amino acids proteinogenic

Table 8.1 Production methods of proteinogenic amino acids.

Of the amino adds isolated from living material, only about 20 are naturally occurring components of proteins. Some of these are shown in Table 8.2. The remainder, non-proteinogenic amino acids, are found as intermediates or end products of metabolism. 

Despite of the disadvantage, that at least one symmetrical dimer is formed as a major side product, mixed Kolbe electrolysis has turned out to be a powerful synthetic method. It enables the efficient synthesis of rare fatty acids, pheromones, chiral building blocks or non proteinogenic amino acids. The starting compounds are either accessible from the large pool of fatty acids or can be easily prepared via the potent methodologies for the construction of carboxylic acids. 

Figure 9.4. Non-proteinogenetic amino acids in NCP s from all archaeological human bones. The values are the averages of all archaeological human bone samples taken together (cf Table 9.1). Dark columns mineral-bound NCP light columns serum proteins. Most non-proteinogenic amino acids are extracted with the serum proteins.

The use of molecular biology methods, described in Section 5.3 seems to be especially worthwhile as it offers novel possibilities of optimization on process adjustment. Directed evolution leads to the formation of new biocatalysts with improved characteristics (selectivity, activity, stability, etc.). Incorporation ofnon-proteinogenic amino acids makes it possible to reach beyond the repertoire of building blocks used by nature. The prospect of bioconjugate preparation offers the possibility to form functional clusters of enzymes and to perform multiple synthetic steps in one pot. 

Amino acids and amides All 20 proteinogenic amino acids, aminobutyric acid, homoserine, cysrathionine, mugineic acid phytosiderophores (mugineic acid, deoxymugineic acid, hydroxymugineic acid, epi-hydroxymugineic acid, avenic acid, distichonic acid A)... 

L-piperidine-2-carboxylic acid is a non-proteinogenic amino acid that is a metabolite of lysine. The zinc complexes of DL-piperidine-2-carboxylic acid, DL-piperidine-3-carboxylic acid, and piperidine-4-carboxylic acid have been studied. The X-ray crystal structures have been determined for the latter two. [ZnCl2(DL-piperidine 3-carboxylate)2] (42) is monomeric with a tetrahedral metal center and monodentate carboxylates. [Zn2Cl4(piperidine-4-carboxylate)2] (43) contains two bridging carboxylates in a dimeric structure. IR studies suggest that the DL-piperidine-2-carboxy-lato zinc has monodentate carboxylate ligands coordinating.392... 

An alternative to extraction crystallization is used to obtain a desired enantiomer after asymmetric hydrolysis by Evonik Industries. In such a way, L-amino acids for infusion solutions or as intermediates for pharmaceuticals are prepared [35,36]. For example, non-proteinogenic amino acids like L-norvaline or L-norleucine are possible products. The racemic A-acteyl-amino acid is converted by acylase 1 from Aspergillus oryzae to yield the enantiopure L-amino acid, acetic acid and the unconverted substrate (Figure 4.7). The product recovery is achieved by crystallization, benefiting from the low solubility of the product. The product mixture is filtrated by an ultrafiltration membrane and the unconverted acetyl-amino acid is reracemized in a subsequent step. The product yield is 80% and the enantiomeric excess 99.5%. 

Ager, D.J., Li, T., Pantaleone, D.P. et al. (2001) Novel biosynthetic routes to non-proteinogenic amino acids as chiral pharmaceutical intermediates. Journal of Molecular Catalysis B, Enzymatic, 11 (4—6), 199-205. 

The interesting list of molecules in Table 3.3 includes one amino acid in the group of molecules with more than 10 atoms it is the simplest proteinogenic amino acid, glycine. 

Another example of the ability of proteinogenic amino acids, small peptides, and amines to catalyse the formation of new C-C bonds has been demonstrated by Weber and Pizzarello they were able to carry out model reactions for the stereospecific synthesis of sugars (tetroses) using homochiral L-dipeptides. The authors achieved a D-enantiomeric excess (ee) of more than 80% using L-Val-L-Val as the peptide catalyst in sugar synthesis (in particular D-erythrose) via self-condensation of glycol aldehyde. 

The proteinogenic amino acids are distinguished from all others by two characteristic features. They are ... 

The above reactions are shown schematically in Fig. 5.1. The overall reaction is reversible but is, however, shifted to the right, since the enzyme pyrophospho-rylase hydrolyses the diphosphate formed, thus removing it from the equilibrium. Each of the 20 proteinogenic amino acids has at least one specific synthetase. In steps 1 and 2, the amino acid exists in two different forms—in step 1 as a mixed anhydride ... 

The still hypothetical RNA world must fill the gap. Orgel suspects that, in this still dark phase of chemical and molecular evolution, a class of molecules was present which could have been relatively easily formed under the conditions present on the young Earth, and which was found in rocks from meteorites perhaps amino acids. These need not to have been the 20 proteinogenic amino acids which we know today, and which are in part quite complex, such as phenylalanine, histidine and tryptophane simple examples would have sufficed. 

N-Boc-2-Bromoglycine tert-butyl ester (1), introduced Steglich and coworkers, is a versatile synthon for electrophilic glycine,5 an tnpcDortant tool in the synthesis of non-proteinogenic amino acids. 

T. Szyperski, Biosynthetically directed fractional 13C labeling of proteinogenic amino acids an efficient analytical tool to investigate intermediary metabolism. Eur. J. Biochem. 232, 433 448 (1995). 

M Schutkowski, C Mrestani-Klaus, K Neubert. Synthesis of dipeptide 4-nitroanilides containing non-proteinogenic amino acids, (p-nitrophenylisocyanatc) Int J Pept Prot Res 45, 257, 1995. 

Fig. 11.1 Mirror-image relationship ofthe amino acids. All amino acids except glycine) can exist in one of two mirror-symmetric forms, called enantiomers. Proteinogenic amino acids are almost exclusively the L-enantiomer. With some exceptions, biopolypeptides fold into right-handed a-helices. [1,2] In all cases,...

Based on our current understanding of ribosomal protein synthesis, several strategies have been developed to incorporate amino acids other than the 20 standard proteinogenic amino acids into a peptide using the ribosomal machinery . This allows for the design of peptides with novel properties. On the one hand, such a system can be used to synthesize nonstandard peptides that are important pharmaceuticals. In nature, such peptides are produced by nonribosomal peptide synthetases, which operate in complex pathways. On the other hand, non-natural residues are a useful tool in biochemistry and biophysics to study proteins. For example, incorporation of non-natural residues by the ribosome allows for site-specific labeling of proteins with spin labels for electron paramagnetic resonance spectroscopy, with... 

Structure and Function of Peptidyl Carrier Protein Domains Structure and Function of Adenylation Domains Structure and Function of Condensation Domains Structure and Function of Thioesterase Domains Multidomain NRPS Structural Information PCP-C didomain structure PCP-TE didomain structure Structure of a C-A-PCP-TE termination module Pathways to Nonproteinogenic Amino Acids Incorporated into NRP Natural Nonproteinogenic Amino Acids Present as Cellular Metabolites Modification of Proteinogenic Amino Acids Nonproteinogenic Amino Acids Derived from Multistep Pathways Tailoring Enzymology in NRP Natural Products Chemical Approaches Toward Mechanistic Probes and Inhibitors of NRPS... 

Enzymatic elaboration of proteinogenic amino acids is the most common pathway to nonproteinogenic amino acids. Six representative examples are illustrated in Figure 14(b). Amino acids that have undergone oxidation... 

Methionine (Met or M) ((5)-2-amino-4-(methylsulfanyl)-butanoic acid) is a nonpolar, neutral, amino acid with the formula HOOCCH(NH2)CH2CH2SCH3. Together with Cys, Met is one of the two sulfur-containing proteinogenic amino acids and a great antioxidant. Its derivative 5-adenosyl methionine (SAM) serves as a methyl donor. ... 

Threonine (Thr or T) ((2S,31( )-2-amino-3-hydroxybutanoic acid) has an aliphatic hydroxyl side chain and is classified as a polar, uncharged amino acid with the formula HOOCCH(NH2)CHOHCH3. Together with Ser and Tyr, Thr is one of the three proteinogenic amino acids bearing an alcohol group. Thr can be seen as a hydroxylated version of Val. With two chiral centers, Thr can exist in four possible stereoisomers, or two possible diastereomers of L-Thr. However, the name L-Thr is used for one single enantiomer, (2S, 3if)-2-amino-3-hydroxybutanoic acid. The second diastereomer (2S,3S), which is rarely present in nature, is called L- //o-Thr. 

The natural amino acids are mainly a-amino acids, in contrast to (3-amino acids such as p-alanine and taurine. Most a-amino acids have four different substituents at C-2 (Ca). The a atom therefore represents a chiral center—I e., there are two different enantiomers (L- and D-amino acids see p. 8). Among the proteinogenic amino acids, only glycine is not chiral (R = H). In nature, it is almost exclusively L-amino acids that are found. D-Amino acids occur in bacteria—e. g., in murein (see p.40)—and in peptide antibiotics. In animal metabolism, D-Amino acids would disturb the enzymatic reactions of L-amino acids and they are therefore broken down in the liver by the enzyme D-amino add oxidase. 

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