Antibiotics amino acid residues differing from

The seven pacidamycins (121—127), which are isolated from the culture filtrates of S. coerukoruhidus are stmcturaHy similar to the mureidomycins. These seven peptidyl nucleoside antibiotics differ in the terminal amino acid residues (238). The biosynthesis of these nucleoside antibiotics is markedly affected by the amino acids added to the culture medium (239). 

Similarities in structure commonly reflect similarities in biogenesis. Consideration of the architectural patterns and structural relationships of natural products enabled Collie, Robinson, Ruzicka and others to discern the biogenetic units from which certain phenolic compounds, alkaloids and terpenes were formed. A survey of the antibiotics indicates that one large collection of these substances can be derived mainly from amino acid residues, another mainly from acetate (or, on occasion, propionate) and a third from simple sugars. Some structures can be dissected into two or more different fragments that are derived from different types of biogenetic unit. 

A number of antibiotics contain amino acid residues that differ structurally from those found in proteins. Examples are ,y-diaminobutyric acid in the polymyxins, D- -aminoadipic acid in cephalosporin N and C, / -methyl-lanthionine in subtilin, nisin and cinnamycin, a-phenylsarcosine and L-a,lV-dimethylleucine in etamycin, (-)-)-, e-diamino-w-caproic acid ( 8-lysine) in streptothricini , and L-jS-methylaspartic acid (which can be formed from... 

Colistin (COL) is a multicomponent antibiotic (polymyxins E) that is produced by strains of inverse Bacillus polymyxa. It consists of a mixture of several closely related decapeptides with a general structure composed of a cyclic heptapeptide moiety and a side chain acetylated at the N-terminus by a fatty acid. Up to 13 different components have been identified. The two main components of colistin are polymyxins El and E2 they include the same amino acids but a different fatty acid (216). A selective and sensitive HPLC method was developed for the determination of COL residues in milk and four bovine tissues (muscle, liver, kidney, and fat). The sample pretreatment consists of protein precipitation with trichloracetic acid (TCA), solid-phase purification on Cl 8 SPE cartridges, and precolumn derivatization of colistin with o-phthalaldehyde and 2-mercaptoethanol in borate buffer (pH 10.5). The last step was performed automatically, and the resulting reaction mixture was injected into a switching HPLC system including a precolumn and the reversed-phase analytical column. Fluorescence detection was used. The structural study of El and E2 derivatives was carried out by HPLC coupled with an electrospray MS. Recoveries from the preseparation procedure were higher than 60%. 

Certain D-amino acids can be formed in bacteria by processes involving a racemase and D-amino acid transaminases. Amino acid activating systems have been found for D-alanine in Staph, aureus and a number of other bac-teria 34 is thus possible that free D-amino acids are sometimes incorporated as such into peptide antibiotics. On the other hand, the D-valine fragment of the penicillins arises from changes in an intermediate peptide that contains an L-valine residue. L-Valine in the culture fluid appears to be the precursor of the D-valine residue found in some of the actinomycins, but this relationship does not reveal the stage at which the inversion of configuration occurs. Differences in the permeability of cells or intracellular structures to l- and D-amino acids are liable to complicate the interpretation of experiments in this field. 

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