Amino acids nonprotein

The amino acids not encountered in protein biosynthesis are heterogenous in their chemical structures. They may be derivatives of chorismic acid (D 8.2) of jS-cyanoalanine (D 9.3), glycine (D 10), L-cysteine (D 11.1, D 11.2), L-methio-nine (D 12), L-asparagine (D 16), L-glutamic acid, L-proline, L-ornithine (D 17), L-lysine (D 18), L-arginine (D 19), L-tryptophan (D 21, D 21.1, D 21.5), L-phenyl-alanine, L-tyrosine (D 22), etc. 

Nonprotein amino acids are usually found in the free state or as part of simple products such as y-glutamyl, acetyl or oxalyl derivatives. They also occur, however, as constituents of small peptides, such as the phalloidins and amanitins (D 23), or as precursors of other secondary products (see formation of glucosinolates, D 9.4). 

More than 400 nonprotein amino acids were found in microorganisms, plants and animals. 

Formation of nonprotein amino acids proceeds either 

The biosynthesis of the seleno amino acids is not fully understood. It seems, however, that selenite and selenate are reduced to hydrogen selenide, which reacts with L-serine or L-homoserine as described for hydrogen sulfide (Dll and D 12). L-Methylselenocysteine and L-selenomethionine may be formed by methyl group transfer. 

Nonprotein Amino Acids Derived from Aspartic Acid Lysine-Derived Nonprotein Amino Acids Pipecolic Acid and Related Compounds L-Mimosine Homoserine L-Canavanine Canaline 

L-Azetidine-2-carboxylic Acid and Related Amino Acids Nonprotein Amino Acids Derived from Isoleucine L-Hypoglycin A and B 

L-Homoarginine and Related Compounds from the Genera Lathyrus and Vida (Fabaceae) 

Amino Acids from 3-Cyano-L-alanine and Asparagine Nonprotein Amino Acids Developed from Glutamic Acid Other Nonprotein Amino Acids Sulfur-Containing Amino Acids Djenkolic Acid L-Indospicine Albiziine 

5-Hydroxy-L-tryptophan 3,4-Dihydroxy-L-phenylalanine (L-dopa) Selenium-Containing Amino Acids Nonprotein Amino Acids in Seeds of the Cucurbitaceae Compounds Involved in Iron Metabolism in Plants Ethylene and Its Precursors 

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The presence of many nonprotein amino acids has been reported in various living metaboUtes, such as in antibiotics, some other microbial products, and in nonproteinaceous substances of animals and plants (7). Plant amino acids (8) and seleno amino acids (9) have been reviewed. 

In addition to the twenty amino acids commonly found in proteins, two others—selenocysteine and pyrrolysine—are found in some organisms, and more than 700 nonprotein amino acids are also found in nature. y-Amino-butyric acid (GABA), for instance, is found in the brain and acts as a neurotransmitter homocysteine is found in blood and is linked to coronary heart disease and thyroxine is found in the thyroid gland, where it acts as a hormone. 

Figure 1. Structures of some nonprotein amino acids isolated from plants...

In mammals, peptide hormones typically contain only the a-amino acids of proteins finked by standard peptide bonds. Other peptides may, however, contain nonprotein amino acids, derivatives of the protein amino acids, or amino acids finked by an atypical peptide bond. For example, the amino terminal glutamate of glutathione, which participates in protein folding and in the metabolism of xenobiotics (Chapter 53), is finked to cysteine by a non-a peptide bond (Figure 3—3). The amino terminal glutamate of thyrotropin-... 

Antibiotic effects of nonprotein amino acids have not been studied in much detail with soil microorganisms. The organs of legumes alone contain more than 300 nonproteinogenic amino acids, such as methylene-glutamine, common to all... 

Table 3 Susceptibility of Yeast Species and Bacterial Strains from Pea Seedlings Against the Heterocyclic Nonprotein Amino Acid P-I.soxylinonyl-Alanine (PlA) ...

Nonprobability sampling, 26 1001 Nonproduct contact utilities, 11 45-46 Nonprotein amino acids, 2 554 Nonprotein nitrogen (NPN), 10 865 Nonquenching photoluminescence properties, 26 804-805... 

Some recovery problems encountered during hydrolytic extraction of amino acids from environmental samples were discussed. A way was proposed for compensating for differential losses of neutral, acidic and basic amino acids, consisting of adding various nonprotein amino acids before the hydrolysis, that act as charge-matched recovery standards131. 

Kataoka (1997) describes a method for the analysis of 21 protein amino acids and 33 nonprotein amino acids with NPD detection. One disadvantage of this method is the use of diazomethane, which is explosive and toxic (Kataoka, 1997). A method for homocysteine with GC-FID analysis uses a one-step derivatization with ethyl chloroformate and an extraction procedure (Husek et al., 2003). 

For the purpose of this chapter, all amino acids containing side chains that differ from the L-a-amino acids will be designated as either unusual or nonprotein amino acids. This is due to the observation that these unusual amino acids are generally not found to be the constituents of proteins. The scope of this chapter is limited to nonprotein L-a-amino acids. The definition of nonprotein amino acid is not absolute and, therefore, the... 

According to the report by Bell et al. there are about 800 nonprotein amino acids known to date in the literature. It is not practical to cite all the primary literature of the reported nonprotein amino acids. To the best of our knowledge, we have tried to cite the most relevant references and the recent review papers available. In most cases, further references for the primary literature can be obtained from these reviews. We apologize to the reader for any missed compounds and citations that might be relevant to the material. 

When the biosynthetic pathways given above are examined, it is apparent that several intermediates are indeed nonprotein ct-amino acids. Ornithine, homoserine, homocysteine, and ct-e-diaminopimelic acid are a few examples. This shows that some nonprotein amino acids originate as intermediates during the biosynthesis of... 

In addition to this, it has been reported that nonprotein amino acids could be formed by structural modifications to protein amino acids (methylation, hydroxylation, and halogenation) through modified L-a-amino acid biosynthetic pathways and through novel biosynthetic routes. Some examples of the nonprotein amino acids derived through these biosynthetic pathways are given below (Figure 3). A detailed discussion of known biosyntheses for certain nonprotein amino acids will be discussed later in this chapter. 

Figure 3 Nonprotein amino acids (a) 5,5,5-trichioroieucine, (b) coronamic acid, and (c) 4-OH-phenylglycine.

Earlier in this chapter, it was mentioned that many of the nonprotein amino acids are components of nonribosomal peptides. During such a biosynthesis, the peptide is attached to a carrier protein through a thioester bond, until chain termination occurs and the final product is released. The carrier protein is posttranslationally modified by the attachment of a phosphopantetheinyl group from coenzyme A. This step gives rise to the active carrier protein with a phosphopantetheine arm upon which amino acids are added to during NRPS. As an example, loading of isoleucine onto the carrier protein is depicted below (Scheme 5). Further details about nonribosomal peptide syntheses and enzymatic reactions can be found in Chapter 5.19. 

During the biosynthesis of nonribosomal peptides, there are two ways to incorporate the nonprotein amino acids. They can be incorporated either as a single unit or as an L-a-amino acid, which then undergoes structural modifications, while attached to the carrier protein. In the case of coronamic acid, L-rr//o-isoleucine is loaded onto the carrier protein and a unique biosynthetic pathway produces a cyclopropyl group containing a nonprotein amino acid. Specific examples of the biosynthesis of nonprotein amino acids will be discussed in the following sections. 

This section focuses on the nonprotein amino acids containing alkyl or haloalkyl groups as side chains. There are number of examples containing linear and branched alkyl chains, such as ethyl, propyl, and t-butyl. Some amino acids contain the cyclopropyl group as side chains (coronamic acid derivatives and BZR-cotoxin 11). Furthermore, dysamides, a class of diketopiperazines, contain nonprotein amino acids with chlorinated alkyl side chains. ... 

The nonprotein amino acid, 1-aminocyclopropane-l-carboxylic acid, is an intermediate of ethylene biosynthesis in plants. This amino acid is synthesized from the L-a-amino acid methionine through the intermediate 5 -adenosyl-L-methionine (SAM) (Scheme 8). ... 

Many of the listed nonprotein amino acids have been identified as components of nonribosomal peptides from fungi and sponges. Hence, they tend to exhibit antifungal and antimicrobial properties, and in some cases potent cytotoxicity is observed. Specific details on known nonprotein amino acids are given in Table 1. 

Table 1 Nonprotein amino acids containing alkyl, cycloalkyl, or haloalkyl side chains...

Nonprotein amino acid with antifungai property 64, 65... 

Isolated from mushroom Nonprotein amino acid with phytotoxic,... 

A number of nonprotein amino acids with unsaturated side chains have been isolated. Many of these contain alkene side chains, but some alkyne side chains containing amino acids have also been identified. Nonprotein dehydroamino acids do not have an a-stereocenter these amino acids are still classified under this category. Dehydroamino acids are generally biosynthesized by the enzymatic elimination of a leaving group at the /3-carbon. For example, serine and threonine are enzymatically dehydrated to give dehydroalanine and dehydrobutyrine, respectively. A similar biosynthetic pathway is hypothesized for dehydroamino acids found in nonribosomal peptides, such as nodularins and microcystins. ... 

Nature utilizes the shikimate pathway for the biosynthesis of amino acids with aryl side chains. These nonprotein amino acids are often synthesized through intermediates found in the shikimate pathway. In many cases, L-a-amino acids are functionalized at different sites to yield nonprotein amino acids. These modifications include oxidation, hydroxylation, halogenation, methylation, and thiolation. In addition to these modifications, nature also utilizes modified biosynthetic pathways to produce compounds that are structurally more complex. When analyzing the structures of these nonprotein amino acids, one can generally identify the structural similarities to one of the L-a-amino acids with aromatic side chains. 

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