Synthesis of Cell Wall Polysaccharides: Plant Cellulose and Bacterial Peptidoglycan:- Lipid-Linked Oligosaccharides Are Precursors for Bacterial Cell Wall Synthesis
Like plants, many bacteria have thick, rigid extracellular walls that protect them from osmotic lysis. The peptidoglycan that gives bacterial envelopes their strength and rigidity is an alternating linear copolymer of N acetylglucosamine (GlcNAc) and N-acetylmuramic acid (Mur2Ac), linked by (β1→4) glycosidic bonds and cross-linked by short peptides attached to the Mur2Ac (Fig. 20–33). During assembly of the polysaccharide backbone of this complex macromolecule, both GlcNAc and Mur2Ac are activated by attachment of a uridine nucleotide at their anomeric carbons. First, GlcNAc 1 phosphate condenses with UTP to form UDP-GlcNAc (Fig. 20–34, step 1), which reacts with phospho enolpyruvate to form UDP-Mur2Ac (step 2); five amino acids are then added (step 3). The Mur2Ac-pentapep tide moiety is transferred from the uridine nucleotide to the membrane lipid dolichol, a long-chain isoprenoid alcohol (see Fig. 10–22f) (step 4), and a GlcNAc residue is donated by UDP-GlcNAc (step 5). In many bacteria, five glycines are added in peptide linkage to the amino group of the Lys residue of the pentapeptide (step 6). Finally, this disaccharide decapeptide is added to the nonreducing end of an existing peptidoglycan molecule (step 7). A transpeptidation reaction cross links adjacent polysaccharide chains (step 8), con tributing to a huge, strong, macromolecular wall around the bacterial cell. Many of the most effective antibiotics in use today act by inhibiting reactions in the synthesis of the peptidoglycan (Box 20–1). Many other oligosaccharides and polysaccharides are synthesized by similar routes in which sugars are activated for subsequent reactions by attachment to nucleotides. In the glycosylation of proteins, for example (see Fig. 27–34), the precursors of the carbohydrate moieties include sugar nucleotides and lipid-linked oligosaccharides.
FIGURE 20–33 Peptidoglycan structure. This is the peptidoglycan of the cell wall of Staphylococcus aureus, a gram-positive bacterium. Peptides (strings of colored spheres) covalently link N-acetylmuramic acid residues in neighboring polysaccharide chains. Note the mixture of L and D amino acids in the peptides. Gram-positive bacteria such as S. aureus have a pentaglycine chain in the cross-link. Gram-negative bacteria, such as E. coli, lack the pentaglycine; instead, the terminal D-Ala residue of one tetrapeptide is attached directly to a neighbor ing tetrapeptide through either L-Lys or a lysine-like amino acid, di-aminopimelic acid.
FIGURE 20–34 Synthesis of bacterial peptidoglycan. In the early steps of this pathway ( 1 through 4 ), N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (Mur2Ac) are activated by attachment of a uridine nucleotide (UDP) to their anomeric carbons and, in the case of Mur2Ac, of a long-chain isoprenyl alcohol (dolichol) through a phosphodiester bond. These activating groups participate in the formation of glycosidic linkages; they serve as excellent leaving groups. After 5, 6 assembly of a disaccharide with a peptide side chain (10 amino acid residues), 7 this precursor is transferred to the nonreducing end of an existing peptidoglycan chain, which serves as a primer for the polymerization reaction. Finally, 8 in a transpeptidation reaction between the peptide side chains on two different peptidoglycan molecules, a Gly residue at the end of one chain displaces a terminal D-Ala in the other chain, forming a cross-link. This transpeptidation reaction is inhibited by the penicillins, which kill bacteria by weakening their cell walls.
