Bacitracins are an example of cyclic peptides having a side chain (Fig. 2). In the molecule of bleomycins, the sugars L-glucose and 3-O-carbamoyl-D-mannose are found. Peptide antibiotics containing an atom of iron or phosphorus in the molecule have also been isolated. If two molecules of cysteine ??are present in the peptide antibiotic, they are linked by a sulfide bridge. Another cyclic polypeptide (heptapeptide) is iturin, an antifungal antibiotic, produced by Bacillus subtilis, effective against plant pathogens [4].
A special type of compounds are enniatines. Their molecule consists of three residues of branched amino acids, L-valine, L-leucine and L-isoleucine, and three residues of D - 2-hydroxyisovaleric acid (D-Hyiv). The amino acids and D-Hyiv are linked by alternating amide and ester bonds. The amide bonds are finally N-methylated .. The biosynthesis of peptide antibiotics takes place on a multienzyme complex [5]. The individual amino acids are activated using ATP to form aminoacyl adenylates. The aminoacyl groups are transferred to the enzyme thiol groups where they are bound as thioesters. The structural arrangement of the thiol groups in the synthetases determines the order of amino acids in the peptide. The formation of peptide bond is mediated by 4-phosphopantetheine, that is an integral part of the multifunctional multienzyme.
The way how the order of the amino acids in the molecule is regulated is not known. It is probably determined by the tertiary configuration of the enzyme. This specificity, however, is not very high since the microorganisms mostly produce a mixture of peptides differing only in one or several amino acids in the chain .. Gramicidin S synthetase is an enzyme consists of two complementary enzymes having molecular weights of 100 kD and 280 kD.synthetase. The enzyme consists of three subunits having molecular weights of 200, 210 and 360 kD [5]. Each subunit contains phosphopantetheine. The enzyme A activates the first five amino acids of bacitracin, the enzyme B activates L-Lys and L-Orn, and the enzyme C activates the other five amino acids. D-amino acids are produced by racemization of their L-forms directly on the enzyme complex. Initiation and elongation start on the subunit A up to the pentapeptide, independently of the presence of the subunits B and C. The pentapeptide is transferred to the subunit B where two other amino acids are added. The heptapeptide is subsequently transferred to the subunit C where the biosynthesis of bacitracin is finished. The cyclization is achieved by binding the asparagine carboxy group to the? -amino Group of lysine, whereas, to the? -amino Group of the same lysine, the isoleucin e carboxyl group is bound.of action. The antibiotic activity of bacitracin results in an efficient inhibition of proteosynthesis and cell wall synthesis but other effects such as an interference with cytoplasmic membrane components and cation-dependent antifungal effects have been observed as well. In the case of gramicidin S, hemolytic effects, inhibition of protein phosphatases and interaction with nucleotides have been observed, in addition to the antibacterial activity. Even though antibiotics normally have several mechanisms of their action, the primary one is thought to be the effect observed at the lowest concentration of all. The peptide antibiotics are efficient mainly against Gram-positive bacteria
? - Lactams.The main representatives of? -lactams are penicil lins and cephalosporins. Penicillins have a thiazoline? -lactam Ring in the molecule and differ, one from another, by side chains linked via the amino group.
Cephalosporins [6] have a basic structure similar to that of penicillins and the derivatives are also formed by a variation of the side chain.
The thiazolidine? -lac tam ring is synthesized using three amino acids: L -? - amino adipic acid, L-cystein and L-valine by? -aminoadipyl- cysteine-valine synthetases. By condensation of these three amino acids, a tripeptide is formed. It is transformed to the molecule of penicilli n or cephalosporin through subsequent transformations. The principial works about enzymes of? -lactams Biosynthetic pathways were done by Abraham and his collegues.
Clavulanic ac id also belongs to? -lactams. This acid has a bicyclic ring structure resemb ling that of penicillin, except that oxygen replaces sulfur in the five-membered ring. Clavulanic acid is an irreversible inhibitor of many? -lactamases. The discovery of clavulanic acid was a starting point for the development of penicillin analogues, abl e to inactivate these enzymes.activity. Penicillins are especially active against Gram-positive bacteria but some semisynthetic penicillins, such as ampicillin, that is lipophilic as compared to, for example, benzyl penicillin, are als...
