Peptides biosynthesis, ribosomal

PEPTIDES, PROTEINS, AND OTHER AMINO ACID DERIVATIVES 

Peptides are produced in nature by one of two methods, termed ribosomal peptide biosynthesis 

A simplified representation of peptide biosynthesis, as characterized in the hacterium Escherichia coli, is discussed in Section 14.2.6. The major aspect to be considered here relates to the bond forming processes involved in linking the amino acids. 

Initially, the amino acid is activated by an ATP-dependent process, producing an aminoacyl-AMP. This may be considered to be nucleophilic attack of 

Carboxylate is not an especially good nucleophile, but we have seen it used in Sn2 reactions to synthesize esters (see Section 6.3.2). Here, attack is 

The intermediate aminoacyl-AMP can also be seen to be an anhydride, but in this case a mixed anhydride of carboxylic and phosphoric acids (see Box 7.27). This can react with a hydroxyl group in ribose, part of 

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The amino acid components of proteins have the L conhguration (see Section 3.4.10), but many peptides are known that contain one or more D-amino acids in their stmctures. o-Amino acids are not encoded by DNA, and peptides containing them are produced by what is termed non-ribosomal peptide biosynthesis (see Section 13.5.2). o-Amino acids generally arise by epimerization of L-amino acids (see Box 10.10). All the protein L-amino acids have the S conhguration, except for glycine, which is not chiral, and L-methionine which is R, a consequence of the priority mles for systematic descriptors of conhguration (see Section 3.4.10). 

ACV is produced by the modular system for non-ribosomal peptide biosynthesis. The amino acid precursors are L-a-aminoadipic acid (an unusual amino acid derived by modification of L-lysine), L-cysteine, and L-valine during tripeptide formation, the L-valine is epimerized to o-valine (see Box 10.10). 

Antibiotics that interfere with ribosomal peptide biosynthesis... 

T Stachelhaus, HD Mootz, V Bergendahl, MA Marahiel. Peptide bond formation in non-ribosomal peptide biosynthesis catalytic role of the condensation domain. J Biol Chem 273 22773-22781, 1998. 

NRPS (non-ribosomal peptide synthetase) genes. For further information on non-ribosomal peptide biosynthesis, see Schwarzer, Finking, and Marahiel (2003), Dorrestein and KeUeher (2006) and Wenzel et al. (2006). 

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