Peptides cyclic microbial

During the decade that followed the end of the Second World War Great Britain stepped into the forefront of peptide research. The insulin studies of Sanger (Plate 38) and his associates in Cambridge (cf. p. 158) had a major impact on the entire field of peptide and protein chemistry. In the same period elucidation of the structure of cyclic microbial peptides by A.J.P. Martin (Plate 31) and R.L.M. Synge (Plate 44) and the structural work of E. Abraham and C.G.F. Newton in Oxford on penicillins, and later on cephalosporins, provided a similar stimulus for the development of peptide research. 

A nonribosomal biosynthetic pathway is clearly indicated for CyA, considering its cyclic structure, the partial N methylation of the 11 peptide bonds, the uncommon building units Bmt, L l-aminobutyric acid, and D-alanine, and the plethora of isolated congeners. Nonribosomal biosynthesis directed by multieniyme thiotemplates have been reported for other small peptides of microbial origin, such as gramicidin S and enniacin (for a review, see Ref. 39). 

Non-ribosomally processed peptides represent a large class of natural products of microbial origin. Pharmaceutically important examples are antibiotics of the beta-lactam type (e. g., cephalosporin C) and glycopeptides of the vancomycin class as well as the immunosuppressant cyclic undecapeptide cyclosporine (Fig. 3.4). 

Cyanobacteria known to produce hepatotoxins include species of Microcystis (32-36), Anabaena (37-40), Nostoc (41,42), Oscillatoria (43,44) and the brackish water Nodularia spumigena (45,46). These cyanobacteria produce a wide range of toxins including neurotoxic alkaloids, lipopolysaccharides, phenolic compounds and most importantly, the cyclic hepatotoxic peptides microcystins and nodularins. Since both microcystins and nodularins were recently discovered even in shellfish (47) and tropical fish species (48), and a nodularin variant was isolated in Papua New Guinea also from the tropical marine sponge Theonella swinhoei (49), marine prokaryotes are apparently producing identical toxins as the cyanobacteria. However, since this nodularin variant was isolated from a marine sponge it may well be produced by a microbial symbiont. 

If one of the amino acid residues in a reverse turn has a configuration different from that of the other residues, then the hydrogen bond formed is more kable. In proteins and in the majority of biologically active peptides (which are usually cleavage products of proteins) only L-residues are present, but in microbial peptides D-residues are quite common. It is not surprising, therefore, that most of them have cyclic structures ring closure is very much facilitated by reverse turns. 

Architecture of Microbial Peptides - The cyclic character is the earliest recognized general feature of peptide antibiotics. Open chain peptide antibiotics are rare exceptions (gramicidin A, bottromycin ). The best studied exan le of peptide antibiotics, gramicidin S (I), was recently the... 

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