Why is peptidoglycan synthesis

• Why is peptidoglycan synthesis so important for bacteria:-

The peptide chain can be cross-linked to the peptide chain ofanother strand forming the 3D mesh-like layer. Peptidoglycan servesa structural role in the bacterial cell wall, giving structuralstrength, as well as counteracting the osmotic pressure of thecytoplasm.

• Describe the major steps in peptidoglycan synthesis and notewhich steps can be targeted by antibiotics :-

The peptidoglycan monomers are synthesized in the cytosol andare then attached to a membrane carrier bactoprenol. Bactoprenoltransports peptidoglycan monomers across the cell membrane wherethey are inserted into the existing peptidoglycan.

In the first step of peptidoglycan synthesis, glutamine, whichis an amino acid, donates an amino group to a sugar, fructose6-phosphate. This turns fructose 6-phosphate intoglucosamine-6-phosphate. In step two, an acetyl group istransferred from acetyl CoA to the amino group on theglucosamine-6-phosphate creating N-acetyl-glucosamine-6-phosphate.In step three of the synthesis process, theN-acetyl-glucosamine-6-phosphate is isomerized, which will changeN-acetyl-glucosamine-6-phosphate toN-acetyl-glucosamine-1-phosphate.

In step 4, the N-acetyl-glucosamine-1-phosphate, which is now amonophosphate, attacks UTP. Uridine triphosphate, which is apyrimidine nucleotide, has the ability to act as an energy source.In this particular reaction, after the monophosphate has attackedthe UTP, an inorganic pyrophosphate is given off and is replaced bythe monophosphate, creating UDP-N-acetylglucosamine (2,4). (WhenUDP is used as an energy source, it gives off an inorganicphosphate.) This initial stage, is used to create the precursor forthe NAG in peptidoglycan.

In step 5, some of the UDP-N-acetylglucosamine (UDP-GlcNAc) isconverted to UDP-MurNAc (UDP-N-acetylmuramic acid) by the additionof a lactyl group to the glucosamine. Also in this reaction, the C3hydroxyl group will remove a phosphate from the alpha carbon ofphosphoenolpyruvate. This creates what is called an enol derivativethat will be reduced to a “lactyl moiety” by NADPH in step six.

In step 7, the UDP–MurNAc is converted to UDP-MurNAcpentapeptide by the addition of five amino acids, usually includingthe dipeptide D-alanyl-D-alanine. Each of these reactions requiresthe energy source ATP.This is all referred to as Stage one.

Stage two occurs in the cytoplasmic membrane. It is in themembrane where a lipid carrier called bactoprenol carriespeptidoglycan precursors through the cell membrane. Bactoprenolwill attack the UDP-MurNAc penta, creating a PP-MurNac penta, whichis now a lipid. UDP-GlcNAc is then transported to MurNAc, creatingLipid-PP-MurNAc penta-GlcNAc, a disaccharide, also a precursor topeptidoglycan. How this molecule is transported through themembrane is still not understood. However, once it is there, it isadded to the growing glycan chain.The next reaction is known astranglycosylation. In the reaction, the hydroxyl group of theGlcNAc will attach to the MurNAc in the glycan, which will displacethe lipid-PP from the glycan chain. The enzyme responsible for thisis transglycosylase.

• What are the characteristics of an effective antibiotic drug:-

An ideal antibiotic is an antibacterial agent that kills orinhibits the growth of all harmful bacteria in a host, regardlessof site of infection without affecting beneficial gut microbes (gutflora) or causing undue toxicity to the host.

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