Decent Essays

The peptide antibiotic Bacitracin:

Bacitracin is a cyclic polypeptide antibiotic that was first discovered in 1945 by Johnson et al. and is produced as a mixture of different similar peptides by certain strains of Bacillus subtilis and Bacillus lichenformis. The main compound is bacitracin A and its structure can be seen in Figure X. (Johnson 1945, Strominger 1971, Konz 1997). It is produced nonribosomally by a multienzyme complex composed of the three bacitracin synthetases BA1-3 by a so called thiotemplate mechanism. In this mechanism, adenylated amino acids are activated by hydrolysis of AMP and added to the enzyme, where it is bound as a thioester on the covalently bound 4-phosphopentatheinyl-cofactor. The polypeptide is then produced in a series of transpeptidation reactions (Konz 1997).

Figure X: Sequence and structure of Bacitracin A. The amino acids from L-Lys to L-Asn form the heptapeptide ring and the second cysteine forms the thiazoline ring with the backbone.

The mechanism by which bacitracin inhibits cell growth is by targeting the cell wall synthesis. This is achieved by binding to undecaprenol-pyrophosphate (UPP, C55-PP), which functions as a lipid carrier of peptidoglycan (PG) intermediates during the synthesis of the cell wall, transporting the intermediates from one side of the membrane to the other. …show more content…

The cycle starts with UP, which is produced by dephosphorylation of UPP either through recycling or from de novo synthesis. UPP is then coupled to activated MurNAc-pentapeptide by MraY and activated GlcNAc is added by MurG in a second step to form Lipid II. This is transported across the membrane by the flippase FtsW and the GlcNAc-MurNAc-pentapeptide is transferred to the growing peptidoglycan chains. The UPP in the outer leaflet has to be dephosphorylated and transported back to the inner leaflet for the cycle to complete. Bacitracin binds to UPP and inhibits

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