o effective against Gram-negative bacteria. This effect is explained by their easier entering the cells of Gram-negative bacteria that have a high lipid content in the cell wall. ? -lactam antibiotics interfere with the synthesis of bacterial cell wall and thus inhibit bacterial growth. Such a mechanism of action does little harm to the macroorganism to which? -lactams Are applied.
Glycopeptides.present several hundreds compounds belonging to glycopeptides are known, including semisynthetic derivatives. The best known of all is vancomycin [20] that is effective against Gram-positive bacteria. This antibiotic is widely used in medicine, especially against? -lactam Resistant microorganisms. Vancomycin is not absorbed from the gastrointestinal tract and is used to treat enterocolitis caused mainly by Clostridium difficile.
Vancomycin is produced by several tens of microorganisms, of which Amycolotopsis orientalis is used for commercial production. Glycopeptides are composed of either seven modified or unusual aromatic amino acids or a mix of aromatic and aliphatic amino acids.
Polyketide-derived antibiotics. A large group of antibiotics includes compounds that are synthesized by polymerization of acetate units and subsequent cyclization of the polyketo chain, that has been formed before or is just being formed, to provide six carbon atoms containing aromatic rings or macrocyclic lactone ring. The terminal group need not be an acetate but also pyruvate, butyrate, ethyl malonate, paraminobenzoic acid, etc. In the early phase, the formation of polyketo chain is similar to that taking place during the biosynthesis of fatty acids, and is catalyzed by the enzyme polyketosynthase. A principal role is played by the Acyl Carrier Protein (ACP) [7]. The ACP prosthetic group in ma ny microorganisms is 4? -phosphopantothenic Acid. Its terminal groups and acyls produced by polymerization are bound via the -SH group. The acyls are transferred to the other -SH group, that is a part of the cysteine ??molecule. Polyketosynthase has not yet b een isolated and its properties have been deduced from the analyses of DNA sequences of cloned genes. Polyketosynthases include two distinct groups located either in domains on multifunctional proteins or present on individual, monofunctional proteins.
6-Methyl salicylic acid .6-Methyl salicylic acid (6MS) represents the simplest polyketide, that is formed by condensation and subsequent aromatisation of one acetylCoA molecule and three malonylCoA molecules. This compound was isolated from Penicillium patulum. By other metabolic steps 6MS is transformed to produce a toxin called patulin. The synthesis of 6MS takes place on an enzymatic complex called 6MS synthetase [7-8].
Tetracyclines . Chlortetracycline and tetracycline are produced by the actinomycete Streptomyces aureofaciens, whereas oxytetracycline and tetracycline by the actinomycete Streptomyces rimosus. The tetracycline molecule is synthesized from one molecule of malonic acid semiamide and eight molecules of malonate. In the early steps, the synthesis is similar to the biosynthesis of fatty acids, but the keto groups are not reduced and aromatic rings are formed to yield 6-methyl pretetramide. This compound is the first known intermediate of the tetracycline biosynthesis that is further transformed to yield one of the tetracycline molecules. As to the enzymes transforming the intermediates of chlortetracycline and tetracycline biosynthesis, the last three have been described: S-adenosylmethionine: 4-dedimethylamino - 4-aminotetracycline N-methyltransferase methylating the amino group in position 4, anhydrotetracycline oxygenase and NADP: tetracycline 5a ( 11a) dehydrogenase (tetracycline dehydrogenase). For more extensive coverage of r esearch, articles by B? Hal and B? Hal and Hunter [8] can by consulted.act as inhibitors of proteosynthesis. They are considered to be wide-spectrum antibiotics, that are efficient against both Gram-positive and Gram-negative bacteria. However, having significant side effects on the human macroorganism, they are preferably used only in the case other, less toxic antibiotics are not effective.
Anthracyclines .Anthracyclines are synthesized in a similar way as other polyketides. They often have one or several sugar residues in the molecule, most often deoxy-sugars, synthesized from glucose, are present in the anthracycline molecule. As to their biological activity, daunorubicin and doxorubicin (adriamycin) are rather important. They are excellent antitumor agents, which are widely used in the treatment of a number of solid tumors and leukemias in human. However, these drugs have dose limiting toxicities such as cardiac damage and bone marrow inhibition. In recent years, a vari...
