Peptides, biosynthesis

Synthesis and biosynthesis of peptides and proteins reqnires the combination of amino acids via amide bonds. We have seen eariier that the chemicai reaction of amines and acids to prodnce a simpie amide is severeiy hindered by initiai sait formation, and that 

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Kopp, F. and Marahiel, M.A. (2007) Macrocyclization strategies in polyketide and nonribosomal peptide biosynthesis. Natural Product Reports, 24, 735. 

Duerfahrt, T., Eppelmann, K., Muller, R. andMarahiel, M.A. (2004) Rational design ofabimodular model system for the investigation of heterocyclization in nonribosomal peptide biosynthesis. Chemistry Biology, 11, 261-271. 

FIGURE 1 8-3 Intracellular pathway of bioactive peptide biosynthesis, processing and storage. Neuropeptide precursors are synthesized on ribosomes at the endoplasmic reticulum and processed through the Golgi. Axonal transport of the large dense-core vesicle to the synaptic site of release precedes the actual secretion. 

Epimerization ofi-amino acids to o-amino acids during peptide biosynthesis... 

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). 

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. 

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). 

Carreras CW, Pieper R, Khosla C (1997) The Chemistry and Biology of Fatty Acid, Polyketide, and Nonribosomal Peptide Biosynthesis. 188 85-126 Ceulemans A (1994) The Doublet States in Chromium (III) Complexes. A Shell-Theoretic View. 171 27-68... 

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