Duramycin

L-Asp hydroxylated at the /3-carbon to generate 7a ro-3-hydroxyl-L-aspartic acid has so far only been detected in cinnamycin and the duramycins, lantibiotics produced by actinomycetes. " This modification has also been found in mammalian proteins, such as the vitamin K-dependent protein C, and the epidermal growth factor (EGF)-like domain in human plasma factor IX. Both bovine and human aspartyl-/3-hydroxylases have been purified and characterized and their in vitro hydroxylation activity has been shown using proteins... 

Duramycin (146) Polycyclic Molil901 Antibacterial (cystic Increases chloride Phase n AOP Orphan in 787-789... 

ShotweU OL, Stodola EH, Michael WR, Lindenfelser LA, Dworschack RCi Pridham TG. (1958) Antibiotics against plant disease. III. Duramycin, anew antibiotic from Streptomyces Cinnamomeus forma Azacoluta. J Am Chem Soc 80 3912-3915. 

Hayashi E, Nagashima K, Terui Y, Kawamura Y, Matsnmoto K, Itazaki H. (1990) The structur of PA48009 The revised structure of duramycin. J Antibiot 43 1421-1430. 

NMR studies have been used to resolve the structures of several lantibiotics.38 Cinnamycin and duramycin have been shown to adopt U-shaped globular structures, resulting from their intertwined lanthionine cross-links, which include a head-to-tail thioether.38 The structures are amphipathic, with hydrophobic residues clustered around the bend of the U-shaped and hydrophilic residues located around the termini. Likewise, the type B peptides mersacidin and actagardine adopt well-defined globular folds in methanol and water acetonitrile mixtures.39 40... 

Currently, the most common commercial application for lantibiotics is as a preservative in the food industry to combat food-home pathogens and spoilage bacteria, but many other uses are under active investigation. Duramycin has been shown to increase chloride transport in nasal epithelial cells of cystic fibrosis patients (13), which in turn increases the fluidity of mucus in the lungs and airway and decreases the patient s susceptibility to infections. Furthermore, several lantibiotics have shown potent activities against multidrug resistant pathogenic bacterial strains. Combined with the development of new techniques to alter the structures of lantibiotics, the future will likely see detailed SAR studies that may result in improved variants. 

Cloutier MM, Guernsey L, Sha afi RI. Duramycin increases intracellular calcium in airway epithelium. Membr Biochem 1993 10(2) 107-18. 

The inspection of cinnamycin (4) and duramycin (5)—prompted by their content in lanthionine and /3-methyllanthionine—for the presence of ,/3-unsaturated amino acids was negative. However, cinnamycin as well as duramycin contain lysinoalanine, among other amino acids rarely seen in nature. Did the peptides at one time contain dehydroalanine and did it serve as a precursor for lysinoalanine If the answer to this question were yes, which amino acids, in turn, are potential precursors of dehydroalanine ... 

The amino acid compositions of cinnamycin and duramycin differ by the exchange of one residue of arginine in the former and by a residue... 

Figure 13. Formation of lysinoalanine in cmnamycin and duramycin. Question mark indicates the uncertainty presently existing about the number of peptide bonds between the alanine and lysine moiety in lysinoalanine.

The enthusiasm and effort of able co-workers produced the results discussed here. John L. Morell determined the structure of nisin, H. H. Kiltz and E. Nebelin that of subtilin. H. H. Kiltz initiated the studies on cinnamycin, since then advanced by H. C. Chen and C. H. Chapin. Judith H. Brown is responsible for the information about duramycin. The studies on lysinoalanine are being continued by J. H. Brown, S. Nanno, and C. H. Chapin. 

Duramycin S. cinnamoneus Gram-pos. bacteria, fungi, yeast Asp. Glu, Gly, Phe, Pro, Val, Lanthionine, p-methyl-lanthioninc ... 

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