Antibiotics bacteria producing peptide

Thiopeptin is a sulfur-containing peptide antibiotic complex produced by Streptomyces tateyamensis. It is composed of five closely related components, the thiopeptins Ai, A2, A3, A4, and B (8). Commercially available thiopeptin is primarily composed of thiopeptins B. This antibiotic is active against gram-positive bacteria and is used exclusively as a feed additive for pigs. 

In addition to the 20 amino acids most frequently found in proteins a large group of amino acids occur in plants, bacteria, and animals that are not found in proteins. Some are found in peptide linkages in compounds that are important as cell wall or capsular structures in bacteria or as antibiotic substances produced by bacteria and fungi. Others are found as free amino acids in seeds and other plant structures. Some amino acids are never found in proteins. These nonprotein amino acids, numbering in the hundreds, include precursors of normal amino acids, such as homoserine and diaminopimelate intermediates in catabolic pathways, such as pipecolic acid d enantiomers of normal amino acids and amino acid analogs, such as azetidine-2-carboxylic acid and canavanine, that might be formed by unique pathways or by modification of normal amino acid biosynthetic pathways. 

In 1972 the team of Professor Zaehner at Tubingen described a Streptomyces strain producing a novel compound with antibiotic properties. The antibiotic tripeptide produced by Streptomyces viridochromogenes consists of two alanine residues and a novel amino acid that was named phosphinothricin [14] (Fig. 6.3.2). Owing to its structural analogy to glutamate Bayer et al. [14] tested and proved the hypothesis that phosphinothricin acts as an inhibitor of bacterial GS enzyme, whereas the tripeptide phosphinothricyl-alanyl.alanine did not inhibit the isolated GS enzyme. Nevertheless the tripeptide was 1.000-10.000-fold more active in its growth inhibitory effect on different bacteria. The discrepancy is explained by the observation that free phosphinothricin cannot be taken up efficiently by bacteria, whereas the tripeptide is taken up into the bacteria by peptide carriers and, subsequently, the tripeptide is cleaved. 

The jS-lactam antibiotics are believed to act as acylating agents which mimic small peptides involved in bacterial cell wall synthesis. Some bacteria produce enzymes named jS-lactamases which readily cleave the jS-lactam ring, thereby inactivating the drug. The discovery of this form of drug resistance has led to the search for jS-lactamase-stable compounds. 

Pore-Forming Toxins (Proteins and Peptides TC l.C.) represent a group of proteins that have considerably expanded over the last few years within the lactic acid bacteria group (Table 4.2). The production of bacteriocins is a very desirable trait with biotechnological applications. Bacteriocins are bacterially produced peptide antibiotics with the ability to kill a limited range of bacteria, usually but not always those that are closely related to the producer bacterium. 

It is now well understood that all glycopeptide antibiotics exert antibiotic activity against Gram-positive bacteria because they stereospecifically bind to the precursor peptidoglycan peptide terminus A-acyl-o-alanyl-D-alanine produced during bacterial... 

Enramycin is also a linear-ring peptide antibiotic produced by Streptomyces fungicidicus. Enramycin consists of two main components called enramycin A and enramycin B. It is active against gram-positive and acid-fast bacteria and is an approved growth promoter for poultry and swine. Enramycin is usually incorporated in feeds in the form of its monohydrochloride form. 

Chloramphenicol. Chloramphenicol (Chloromycetin) is a synthetically produced agent that exerts antibacterial effects similar to those of erythromycin that is, it binds to the 50S subunit of bacterial ribosomes and inhibits peptide bond formation. Chloramphenicol is a broad-spectrum antibiotic that is active against many gram-negative and gram-positive bacteria. This drug is administered systemically to treat serious infections such as typhoid fever, Haemophilus infections such as osteomyelitis, rickettsial infections such as Rocky Mountain spotted fever, and certain forms of meningitis. Chloramphenicol may also be administered topically to treat various skin, eye, and ear infections. 

There are many examples of peptides that cannot form transmembrane channels on their own but can do so through aggregation. The gramicidin antibiotics, produced by bacteria as part of their chemical defence system, are only 1.6 nm or so in length [11], Specific placement of side chains, such as four tryptophan residues towards the C-terminus, ensures that the helix penetrates cell membranes to a particular depth but does not pass through the membrane. 

Finally, bacitracins are peptide antibiotics produced by Bacillus subtilis and B. licheniformis. Over 20 components are contained in the bacitracin complex medium, among which the major active components are bacitracin A and F (Fig. 3). They exhibit an inhibitory activity against Gram-positive bacteria and are among the most commonly used antibiotics as animal feed additives. 

Polyketide and non-ribosomal peptides produced by bacteria and fungi often attain the conformations that establish biological activity by cychzation constraints introduced by tailoring enzymes. This includes heterocychzation of cysteines, serines and threonines in non-ribosomal peptides. The second cychzation constraint is macrocychzation in polyketides, such as the above-mentioned antibiotic erythromycin and the antitumor epothilones. Regio- and stereospecific macrocychzation usuaUy occurs at the end of the polyketide and non-ribosomal peptide assembly hnes during chain release by thioesterase domains [49]. However, in the case of antibiotics of the ansamycin class, like the antitubercular drug rifamycin, the final... 

Manduca larvae treated with canavanine produce antibiotic peptides in which arginine is replaced by canavanine. Their intrinsic biological activity is greatly diminished and these larvae may be unusually susceptible to infection by bacteria (P. E. Dunn, personal communication). 

The D-enantiomeric amino acids form by nonprotein synthesis inside bacteria in the form of peptide antibiotics. Although proteins predominate in today s DNA world, one assumes that proteins were in a minority at the beginning of the RNA world. It is likely that several pathways independently produced the first smaller peptides early on. Many essential coenzymes consist not only of nucleotide derivatives but also amino acids Coenzyme A, NADH+, S-adenosyl-methionine, tetrahydrofolate, and many more, see below. 

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