Biosynthesis of the pseudomurein

The first steps of murein biosynthesis take place in the cytoplasm, whereas the two final steps occur at the inner and outer face of the cytoplasmic membrane, respectively [38]. This may also be true for the pseudomurein, according to a tentative scheme of the biosynthesis of pseudomurein (Fig. 4) [39-43], proposed on the basis of the structure of putative precursors isolated from cell extracts. 

The synthesis of the pentapeptide moiety is supposed to start with a UDP-activated glutamic acid residue followed by the stepwise formation of UDP-activated peptides up to a pentapeptide. UDP was directly linked to the -amino group of the glutamic acid residue, a type of activation of amino acids previously not found in nature. Finally, the UDP-activated pentapeptide is linked to the disaccharide to give a UDP-activated disaccharide pentapeptide. 

The participation of a nucleotide-activated disaccharide and UDP-activated peptide intermediates are unique features of pseudomurein biosynthesis. Usually, oligosaccharide precursors of bacterial cell-wall polymers are formed at the lipid stage [38,44] and amino acids carrying a nucleotide residue at the. /V -amino group have not been found in nature so far. The distinct differences between the two biosynthetic routes support the hypothesis that murein and pseudomurein represent independent inventions made after the domains bacteria and archaea had been separated from each other during evolution [40,46]. 

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