Amino Acids in Peptides

Bacteria are known to make use of D-amino acids in several peptide antibiotics in which the "wrong" amino acids D-glutamate, D-phenylalanine, D-aspartate, and D-valine were found to be incorporated. It is important to note that the classical biosynthetic pathway in which DNA codes for the twenty L-amino acids of proteins cannot produce these exceptional D-amino acid-containing peptides. DNA does not code for D-amino acids. D-Amino acid containing peptides, on the contrary, are formed by specific biosynthetic routes that have nothing in common with usual protein synthesis. Bacteria implement D-a-alanine and D-glutamate not only in specific peptides, but also in the cell wall peptidoglycan layer (Nagata et al. 1998).

Moving from bacteria to eukaryotes, the peptide dermorphin serves as an example of a protein that makes use of a D-amino acid.2 The small tetrapeptide achatin I

2003). In honey samples that usually contain 100 mg amino acids per 100 g honey, d-phenylalanine was found at up to 3%, and d-leucine up to 4%. In tea samples, the d-enantiomer of theanine, an amino acid commonly found in tea, was identified at up to 3%. Formosa Oolong tea even contained 13% d-theanine. Roasted cocoa beans, cocoa powder, chocolate, and cocoa shells include d-amino acids and in particular d-proline was found in amounts up to 37% (Patzold and Br├╝ckner 2006). As expected, the quantities of d-amino acids increased on heating of the cocoa samples.

2 Dermorphin was isolated from skin secretions of the South and Middle-American frog Phyl-lomedusinae. It is an opioid peptide of a total of seven amino acid residues including one d-a-alanine molecule. The biological activity of dermorphin was found to be 1 000 times higher than that of morphine. Substituting the d-a-alanine with an l-a-alanine residue provokes loosing the is an example of a peptide that includes the D-enantiomer of phenylalanine.3 A similar variation in the biological activity of a snail protein was reported for the peptide fullicin. Fullicin that includes a D-asparagine residue shows higher bioactivity compared to fullicin containing asparagine's L-enantiomer.

Moving to higher peptides, we can refer to m-agotoxin that was isolated from the toxin of a spider and contained 48 amino acid residues. The amino acid serine at position 46 of m-agotoxin was shown to be present in D-configuration.

At Himeji and Tokyo Institute of Technology, Yoko Nagata and her team followed an interesting hypothesis by investigating the occurrence of peptidyl D-amino acids among various organisms. She compared individual contents of D-amino acids for bacteria, archaea, and eukaryotes. At the beginning of the study, it seemed to her that D-amino acids widely distributed among bacteria have nearly been eliminated in eukaryotes during the evolution of these organisms. The few remaining examples of D-amino acids in eukaryotes were given above in this paragraph. If enantioselec-tive analyses of different types of organisms confirmed this assumption, these results would indicate that the first organisms such as archaea may have used D-amino acids for their molecular architecture of biopolymers in an equivalent manner to L-amino acids and that the symmetry towards the exclusive use of L-amino acids in proteins today was violated only later, i.e., during evolution of eukaryotes. However, Nagata's team's results showed that bacteria and archaea, as well as eukaryotes, contain amounts of peptidyl D-amino acids in the soluble fraction which are not large but are comparable with each other (Nagata et al. 1998). Hence, these results could not be used to verify the attractive hypothesis on the evolutionary elimination of D-amino acids in eukaryotes.

How do we then interpret today's small but general occurrence of D-amino acids in the various domains of life such as bacteria, archaea, and eukaryotes? Were all these D-amino acids produced by successful mutations during biological evolution and racemization of L-amino acids meaning that the origin of life on Earth was exclusively based on the use of L-amino acids? Or are these D-amino acids molecular relicts of an ancient and parallel existing mirror-image life? This question remains difficult to answer (see Sect. 3.4), especially because ubiquitous L-amino acids of living organisms seem to have contaminated all niches of Earth erasing most molecular traces of any mirror-image life.

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